scholarly journals Seven Year Follow up and Comparison of Dosing Strategies from the Pivotal Phase II Clinical Trial of Lenalidomide Plus Rituximab (R2) in Previously Untreated Follicular Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1594-1594
Author(s):  
Nathan H. Fowler ◽  
Preetesh Jain ◽  
Loretta J. Nastoupil ◽  
F. B. Hagemeister ◽  
Sheryl G Forbes ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Follicular Lymphoma ◽  
Board Of Directors ◽  
Research Funding ◽  
Response Rate ◽  
Event Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Best Response

Abstract Introduction: We have previously reported the results of cohort A from a single arm, phase II clinical trial of lenalidomide with rituximab (R2) as frontline treatment for patients with previously untreated follicular lymphoma (FL), Fowler N et al Lancet Oncology 2014. Recent randomized studies (RELEVANCE) did not demonstrate superiority of either R2 or R-Chemo in untreated, high GELF FL, but follow up is short. We now report outcomes of an additional extended dosing cohort (12 mo of R2) and the long term follow up of the both dosing schedules in untreated FL. Methods: A total of 154 pts were included in the original clinical trial (FL, n=80; MZL, n=31; SLL, n=43). Characteristics were collected at the time of starting R2 treatment. Patients received lenalidomide 20 mg/day on days 1-21 of each 28-day cycle and rituximab 375 mg/m2 on day 1 of each cycle (6 cycles; schedule A) and lenalidomide 20 mg/day on days 1-21 of each 28-day cycle for cycles 1-6 then lenalidomide 10 mg/day on days 2-22 for cycles 7-12 with rituximab 375mg/m2 IV x1 weekly on cycle 1 and day 1 of every subsequent cycle (12 cycles; schedule B). Responders continued treatment for at least 6 but up to 12 cycles. The primary endpoint was overall response rate (ORR); secondary endpoints were complete and partial response (CR, PR), safety, and progression free survival (PFS). PFS was defined as time from starting treatment to disease progression or death, event free survival included time from starting treatment to discontinuation due to any cause and overall survival (OS) was defined from the time of initial diagnosis of FL to death/last follow up. Results: Eighty pts with FL were enrolled in study and followed a median of 86 months. Median age was 58 years (range, 29 to 84); 50% were males. 61% pts had grade 1 FL and 39% had grade 2 FL. Schedule A was administered in 50 pts and schedule B in 30 pts. Seventy seven pts were evaluable for initial response assessment and 76 (98%) responded. The best response rate was 95% (87% CR/CRu). At the time of last follow up, 23 patients experienced disease progression, 13 lost to follow up (all had CR as best response and had completed tx), 4 came off study due to pt choice/financial and 4 due to intolerance (2 arterio-thrombotic event, 1 respiratory failure, 1 intolerance) during therapy. After a median follow up of 86 mo, 23 pts (29%) progressed, 5 yr PFS was 75%. Five yr PFS was 70% and 82% for pts on cohort A vs B respectively (P=.30). Overall, 2 pts died, with a 5 year survival 97%, Figure-1 (A-B). The median event free survival in pts with FL was 85 months with a 5 year EFS of 59%. Subgroup analysis showed no statistically significant difference in PFS with FLIPI score, bulky disease and by initial bone marrow involvement. Pts who achieved CR had significantly longer PFS compared to those who did not achieve CR (not reached vs 78 months; p = 0.004), however the OS was not significantly different between the two groups Figure-1 (C-F). Grade 3 or 4 hematologic AEs included neutropenia (28%), thrombocytopenia (3%), and no anemia. Count recovery occurred in all pts with follow up and/or dose modification. Nine pts developed second primary cancers, including one melanoma in-situ, 3 localized skin cancers, and 2 secondary hematologic malignancies. Conclusions: A combination of lenalidomide with rituximab produced durable responses in pts with FL. At a follow up of 7 years, the majority of pts remain in remission and patients who achieved CR had the best outcomes. Five year PFS may be longer in pts who received 12mo of therapy, but will need larger analysis to confirm. Further studies are ongoing to analyze mutation dynamics and genomic profile to identify molecular biomarkers. Disclosures Fowler: Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Nastoupil:Novartis: Honoraria; Juno: Honoraria; Gilead: Honoraria; TG Therappeutics: Research Funding; Spectrum: Honoraria; Janssen: Research Funding; Merck: Honoraria, Research Funding; Karus: Research Funding; Genentech: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Westin:Apotex: Membership on an entity's Board of Directors or advisory committees; Celgen: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees. Wang:Kite Pharma: Research Funding; Novartis: Research Funding; Pharmacyclics: Honoraria, Research Funding; Dava Oncology: Honoraria; Juno: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MoreHealth: Consultancy; Acerta Pharma: Honoraria, Research Funding. Samaniego:ADC Therapeutics: Research Funding.

Rituximab Combined With Three Cycles Of High Dose Dexamethasone Provides a Long Term Response Rate Similar To That Of Splenectomy In Patients With Immune Thrombocytopenia (ITP) Of Duration Less Than 2 Years

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2310-2310 ◽  
Author(s):  
Christina S Lee ◽  
Allison Imahiyerobo ◽  
Micha Thompson ◽  
Marina Izak Karaev ◽  
Waleed Ghanima ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Plasma Cells ◽  
Response Rate ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Platelet Counts ◽  
Best Response

Abstract Background Adults with newly-diagnosed and persistent ITP usually respond to steroid based treatments such as prednisone but relapse with tapering. One 4-day cycle of Dexamethasone (dex) at 40 mg/day in newly diagnosed ITP resulted in a lasting effect in 50% of patients (pts) in 1 study. An Italian study showed that 3 cycles of dex are better than 1 cycle. Approximately 50% of pts with chronic ITP experience a complete or partial response (CR & PR) to rituximab, yet only 20% of pts have a lasting, unmaintained response after 3 years. Mechanistically, rituximab (which depletes B cells but not plasma cells) and dexamethasone (which may be the most potent anti-plasma cell agent) are a logical combination in treatment of antibody-mediated diseases such as ITP. In 2 studies of newly-diagnosed pts, dex 40mg/day x 4 followed by rituximab was more effective than dex alone (one study added more dex half way through). In our pilot study, pts at Weill Cornell Medical College (WCMC) with all stages of ITP were treated with a combination of rituximab (R) and usually 3 cycles of dex. The outcome of this combination was retrospectively analyzed. Methods Combination of standard-dose rituximab (weekly x 4) and usually 3 4-day cycles of 28mg/m2 (max. 40mg) dex at 2-week intervals (R+3Dex) was explored in 67 pediatric and adult pts with ITP at WCMC. Patients were monitored with CBCs obtained weekly and then at less frequent intervals if a response was achieved. Best response (after 8 weeks to avoid transient effects of dex) was determined. Patients were categorized as CR (platelet count≥100x109/L) or PR (50-100x109/L). Relapse was defined as either two consecutive platelet counts <50x109/L and/or need for additional therapy. The duration of response was calculated from date of first rituximab administration to relapse or latest follow-up as of July 31st 2013. Results Overall, 50 of 67 pts treated with R+3Dex achieved a best response of either a CR (n=43) or a PR (n=7) at 8 weeks or later from start of therapy for an overall response rate of 75%. Seventy-three percent of pts received R+3Dex; variations were primarily in the timing and amount of dex given. Fifteen responders, 9 CRs and 6 PRs, relapsed at a median of 9 months. Seventy percent of the responders (or 52% of all pts treated) maintain a continuous response with platelet counts ≥ 50 x 109/L as of their last visit at a median f/u of 20 months. Kaplan Meier Analysis estimates 44% of all pts treated (Figure) and 59% of responders (Figure) maintained a best response without relapse at 67 months after initiating treatment. If only those with ITP ≤ 24 months are included, the estimated long term response rate is 59% (p=0.0017) versus only 19% for those with a duration of ITP > 24 months (Figure). Of 36 responding children and adults who had ITP ≤ 24 months, 29 continued to respond as of last follow up. Adults initially responded better than children (p=0.0019) but the long-term responses were not different (Figure). Pts achieving a CR had longer response than those achieving a PR. Adverse events related to R+Dex were usually mild-moderate, although 3 pts had serum sickness and 2 had transient colitis. IgG levels fell to below the lower limit of normal for age in 14 of 67 pts, 10 of whom had their IgG levels return to normal. In 6 of 14, IgG levels were < 400 mg/dl, some of whom received IVIG. Fifteen patients had serial BK/JC levels without ever detecting virus. Conclusions R+3Dex provides clearly superior results to rituximab alone. Notably, there was a 75% response rate overall (50/67 pts) compared to 50% with R alone. The 5 year response rate was almost 50% of all patients and 3/5 of responders. In patients who had had ITP for ≤ 2 years, the response is comparable to what has been reported with splenectomy. Specifically the results in the ≤ 2 year group suggest that R+3Dex is an effective way to induce indefinitely normal platelet counts in pts with a “short” duration of ITP. R+3Dex was tolerable although patients had difficulty with 3 cycles of dex. The 21% rate of hypogammaglobulinemia, higher than that seen with R alone, is also evidence of the mechanism of R+3Dex affecting both B cells and plasma cells. The lasting, long-lived, unmaintained responses observed in this study suggest that this combination therapeutic strategy should be further tested in a controlled trial in patients with newly diagnosed, persistent, and early chronic ITP, whether or not they have been previously treated with other agents. Disclosures: Bussel: Sysmex: Research Funding; Cangene: Research Funding; Symphogen: Membership on an entity’s Board of Directors or advisory committees; Shionogi: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Ligand: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; IgG of America: Research Funding; Genzyme: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Amgen: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Final Results of a Phase 2 Study of Bendamustine in Combination with Dexamethasone in Patients with Previously Treated Systemic Light-Chain (AL) Amyloidosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4523-4523
Author(s):  
Galina Grigoriev Lagos ◽  
Suzanne Lentzsch ◽  
Raymond L. Comenzo ◽  
Jeffrey Zonder ◽  
Keren Osman ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Response Rate ◽  
Al Amyloidosis ◽  
Event Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Hematologic Response ◽  
Phase 2 Study ◽  
Organ Response

Abstract Background: No established therapies exist for patients who fail or relapse after initial therapy for AL amyloidosis. Bendamustine has shown potential in treating multiple myeloma, chronic lymphocytic leukemia and non-Hodgkins lymphoma but it has not been well studied in AL amyloidosis. We sought to investigate the efficacy and safety of using Bendamustine in combination with dexamethasone (Ben/Dex) in patients with relapsed AL amyloidosis in a multi-center phase 2 study and present the results of the final analysis. Methods: This Phase IIa clinical trial enrolled 31 patients who had persistent or progressive AL amyloidosis after at least 1 prior therapy. An optimal two-stage Simon design approach was used. Of 13 patients initially enrolled, 3 experienced hematologic partial response (PR), and an additional 16 were treated in the second stage. It was pre-determined that if 9 or more of the 29 patients with evaluable response had hematologic PR or better the treatment would be considered worthy of further development. Evaluable response was defined as patients who completed at least 2 treatment cycles. The primary objective was to determine the rate of partial hematologic response (PR). Secondary objectives included the overall hematologic response rate, organ response rate, toxicity profile, event free survival, and overall survival (OS). Patients received treatment in 28 day cycles with Bendamustine given on day 1 and day 2 (100 mg/m2 IV for CrCl≥60 mL/min, 90 mg/m2 IV for CrCl 59-30 mL/min, 70 mg/m2 IV for CrCl 15-30 mL/min) and dexamethasone 20-40 mg given weekly. Treatment was continued until disease progression or for up to 6 courses after complete response (CR). Reasons for discontinuation also included unacceptable toxicity, patient refusal, and non-response. Results :Of the 31 patients enrolled in the trial, 29 had evaluable responses and completed a median of 4 cycles of therapy (range 2-12) with one patient still undergoing treatment as of 7/1/2016. Median age of enrolled patients was 64 (range 42-78). Primarily involved organs included heart (53%), kidney (36%), nerve (7%), and liver (4%); 18 patients had ≥2 major organs involved. The patients received a median of 1.5 prior treatments (range 1-4) and 13 had received prior autologous stem cell transplants. Of evaluable patients (n=29), 41% had hematologic response to Ben/Dex (3% CR, 17% very good partial response, 24% PR). Of these 13 patients, 6 had a response after only 1 cycle of therapy and the median time to best response was 1 cycle (range 1-6 cycles). The median follow up of patients was relatively long, 18.4 months (range 1.5-41.5) and the median OS has not yet been reached (Figure 1). Event free survival defined as time to death, progression of disease or initiation of new therapy was 9.24 months (range 1.8-18.0) (Figure 2). Only 3 patients discontinued treatment due to disease progression while 8 stopped due to an adverse event (AE) although 5 AEs were only grade 1-2 events. There was 1 death during treatment that was unrelated to the study drug and due to underlying cardiac amyloidosis. The most common drug related all grade AEs included anemia (9%), fatigue (8%), and nausea (7%). Organ response was observed in 5 out of 16 patients with renal involvement and 2 out of the 19 patients with cardiac involvement. Conclusions : Bendamustine in combination with dexamethasone is active treatment in patients with AL amyloidosis who had failed multiple prior therapies and results in a significant hematologic response. Treatment was very well tolerated with a low incidence of severe AE in this delicate patient population. Therefore bendamustine is another treatment approach for AL amyloidosis patients who currently have limited therapeutic options. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Lentzsch: Foundation One: Consultancy; BMS: Consultancy; Celgene: Consultancy, Honoraria. Comenzo:Karyopharm: Research Funding; Prothena: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Zonder:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Prothena: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Pharmacyclics: Other: DSMC membership. Pregja:Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Prothena: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Pharmacyclics: Other: data safety monitoring committee. Landau:Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx/Amgen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy.

scholarly journals Long-Term Outcome of Total Therapy Regimens: Impact of Molecular Subgroups

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3309-3309
Author(s):  
Frits van Rhee ◽  
Maurizio Zangari ◽  
Carolina D. Schinke ◽  
Guido J. Tricot ◽  
Doug Steward ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Low Risk ◽  
Event Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Cure Fraction ◽  
Research Grant

Introduction. Our TT regimens for newly diagnosed multiple myeloma (MM) incorporate novel agents into a sequential treatment program comprising induction, tandem autologous stem cell transplantation and consolidation followed by 3 years of maintenance. Herein, we report the very long-term results in a large cohort of 1986 patients treated on successive TT protocols, the most mature of which (TT1, 2, and 3a) have a median follow-up ranging from 12.8 to 23.1 yrs. Methods. TT1 (1990) was followed by TT2 (1998), which introduced Thalidomide (T) in a randomized fashion. TT3 used bortezomib (V) throughout, with TT3a (2003) and 3b (2006) having different maintenance. TT3a used in year 1 of maintenance V, T and dexamethasone (D) and in years 2 and 3 TD. TT3b introduced lenalidomide (R) during maintenance for 3 years together with V and D. TT4 (2009) only enrolled patients with GEP-defined low risk disease and randomized patients to a standard arm or light arm using a similar regimen as TT3b. TT5 (2009) was specifically designed for patients who have a high 70-gene score and employed a dose dense treatment approach. Finally, TT6 (2009) accrued previously treated, patients irrespective of GEP-defined risk using a treatment schema similar to that used in TT5. Gene expression profiling was used to assign molecular classifications. These include HY (hyperdiploidy), LB (gene expression patterns frequently seen in patients with fewer focal bone lesions), MF (spikes in MAF and MAFB expression), MS (hyperactivation of MMSET +/- FGFR3), PR (over-expression of proliferation-related genes), and CD-1 or CD-2 (different forms of aberrant CCND1 and CCND3 expression). A mixed parametric cure model was used to estimate the proportion of patients with long-term, event-free survival, or the "cure fraction." When using progression free survival (PFS) in the model, the cure fraction is the percent of patients who are likely to never experience relapse based on trends in the survival times that have been observed. When using complete remission duration (CRD) in the model, the model estimates the cure fraction among patients who achieved complete response. Results. The median follow-up on the entire cohort patients was 11.6 years (range: 0.0-27.6) The median overall survival was 9.2 years, with 79.3% and 48.0% having an event-free survival greater than 3 and 10 years, respectively. Overall, patients with GEP70 low risk MM had estimated PFS and CRD cure fractions of 20.1% and 32.7%, respectively. GEP70 high risk MM patients fared much worse with estimated cure fractions of only 8.2 and 11.0%. The estimated PFS- and-CRD based cure fractions increased over time with successive protocols (PFS-cure: 6.0% in TT1 to 27.7% in TT4; CRD-cure: 9.3 to 49.8%). These cure fractions were consistent with the early plateau in the PFS and CRD curves seen at 9 years in TT4 patients. The highest cure fractions were seen in the CD-1 molecular group (34.9 and 40.3%) with intermediate outcomes in the HY (20.1 and 30.0%) and MS (22.8 and 33.5%) groups (Table 1). Surprisingly, low cure fractions were observed in the LB (1.1 and 13.5%) and CD-2 groups (13.5 and 26.4%). CD-1, LB and CD-2 groups had similar 5-yr PFS rates of 60, 60 and 63% respectively, but a steady low rate of relapse was observed in the CD-2 and especially the LB group. These findings were confirmed in a 5-yr landmark analysis showing high PFS and CRD cure fractions in the CD-1 group of 62.7 and 72.3% respectively contrasting to much lower cure fractions in the CD-2 (47.2 and 49.2%) and LB (30.8 and 45.0%) groups. Conclusions. We report excellent long-term outcomes in patients with GEP70 low risk MM and cure fractions in the range of 20-30%. Patients with LB and CD-2 subgroups have lower overall cure rates, despites similar initial 5-yr PFS rates compared to the superior performing CD-1 group, which can be explained by the occurrence of late relapses. Table 1 Disclosures van Rhee: EUSA: Consultancy; Adicet Bio: Consultancy; Takeda: Consultancy; Sanofi Genzyme: Consultancy; Kite Pharma: Consultancy; Karyopharm Therapeutics: Consultancy; Castleman Disease Collaborative Network: Consultancy. Walker:Celgene: Research Funding. Davies:Janssen, Celgene: Other: Research Grant, Research Funding; Amgen, Celgene, Janssen, Oncopeptides, Roche, Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Consultant/Advisor. Morgan:Amgen, Roche, Abbvie, Takeda, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Other: research grant, Research Funding. OffLabel Disclosure: anti-CD38 monoclonal antibody targeting myeloma

Randomised Intergroup Trial of First line Treatment for young Low-Risk Patients (<61 years) with Diffuse Large B-Cell Non-Hodgkin's Lymphoma (DLBCL) with a CHOP-like Regimen with or without the Anti-CD20 Antibody Rituximab – 6-Year Follow-up of the Mint Study of the Mabthera International Trial (MInT) Group

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 111-111 ◽  
Author(s):  
Michael Pfreundschuh ◽  
Evelyn Kuhnt ◽  
Lorenz Trümper ◽  
Anders Osterborg ◽  
Marek Trneny ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Survival Benefit ◽  
Research Funding ◽  
Good Prognosis ◽  
Event Free Survival ◽  
Advisory Committees ◽  
Bulky Disease ◽  
Free Survival ◽  
To Receive

Abstract Abstract 111 Background: The addition of rituximab to CHOP-21 significantly improved clinical outcome in elderly patients with DLBCL (Coiffier et al., 2002). The MInT trial, randomized young good-prognosis patients to receive a CHOP-like regimen or the same CHOP-like regimen plus rituximab, and was stopped early because of superiority of the rituximab arm, and results were published with a median follow-up of 34 months (Pfreundschuh et al., Lancet Oncology 2006; 379-91). Objective: Because the MInT study was the first study to show a survival benefit with the addition of rituximab to a CHOP-like regimen in young good-prognosis patients, extended follow-up is important to determine whether the survival benefit is maintained over time and whether a definitive effect on cure rates can be shown. Methods: In a phase III intergroup study with participating cooperative groups from 18 countries, previously untreated patients (18-60 years) with low-risk DLBCL (age-adjusted IPI 0 or 1, stages II-IV and stage I with bulky disease) were randomized to receive 6 cycles of a CHOP-like regimen (CHEMO) or the same chemotherapy plus rituximab 375 mg/m2, given on day 1 of each 3-week regimen and on days 1, 22, 43, 64, 85 and 106 of the 2-week regimens, respectively (R-CHEMO). Radiotherapy (30-40 Gy) was planned to sites of initial bulky disease and/or extranodal involvement. The primary endpoint was event-free survival (EFS) with events defined as failure to achieve complete remission, progressive disease, relapse, death or additional therapy. The trial was powered to show a 10% difference in EFS rate after 3 years. Results: Between 05/2000 and 10/2003 a total of 823 patients were recruited of whom 396 were allocated to receive CHOP-21, 361 to CHOEP-21, 34 to MACOP-B, and 32 to PMitCEBO with or without rituximab. Toxicity, incidence of adverse events and severe adverse events in the CHEMO and the R-CHEMO arms were not significantly different. After a median follow-up of 70 (0.03-117) months, patients assigned to chemotherapy and rituximab had increased 6-year event-free survival compared with those assigned to chemotherapy alone (74.0% [95% CI 69.0–78.3] vs 55.7% [50.3-60.8]; log-rank p<0·0001), increased 6-year progression-free survival (79.9% [75.1 - 83.8%] vs 63.8% [58.2-68.8]; log-rank p<0.001) and increased overall survival (89.8% [86.0-92.6] vs 80.0% [75.3-83.9; log rank p=0.001). In a multivariate analysis event-free survival was affected by the addition of rituximab (hazard ratio [HR] 0.49, p< 0.001), age-adjusted IPI (HR 1.73, p<0.001), and bulky disease (HR 1.43, p=0.004). Similar effects were observed for OS, while PFS was affected by treatment arm (HR 0.49, p<0.001) and age-adjusted IPI (HR 1.8, p<0.001). As a consequence, a very favorable subgroup (aaIPI=0, no bulky) can be distinguished from a less favorable subgroup (aaIPI=1 and/or bulky disease) among good-prognosis patients treated with rituximab. There were 10 late (>60 months) events after CHEMO (61.4 to 96.1 months), including 4 in the very favorable subgroup, while all 8 late events (67.5 to 105.7 months) after R-CHEMO occurred in the less favorable subgroup only, and none in the very favorable subgroup. Conclusion: Addition of rituximab to a CHOP-like regimen leads to a significant improvement of the outcome in young patients with good-prognosis diffuse large B-cell lymphoma, with significant survival benefit maintained during a 6-year follow-up. However, except in the very favorable subgroup after R-CHEMO, late relapses after 5 years occur. While reduction of treatment in a randomized study like the FLYER trial of the DSHNHL is justified, further progress, e.g. by dose densification (UNFOLDER trial of the DSHNHL) and/ or dose escalation is still warranted for the less favorable subgroup. Supported by Roche, Deutsche Krebshilfe and KML. Disclosures: Pfreundschuh: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Trneny:Roche: Honoraria, Research Funding. Walewski:Roche: Honoraria, Research Funding. Pettengell:Roche: Honoraria. Jäger:Roche: Honoraria, Research Funding. Lopez-Guillermo:Roche: Consultancy.

Impact of Additional Cytogenetic Abnormalities and Complex Karyotype on Event-Free Survival in Acute Promyelocytic Leukemia: Analysis from a Single Academic Center Plus the APML4 Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 34-35
Author(s):  
Zachary D. Epstein-Peterson ◽  
Sridevi Rajeeve ◽  
Andriy Derkach ◽  
Jae H. Park ◽  
Eytan M. Stein ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Acute Promyelocytic Leukemia ◽  
Research Funding ◽  
Promyelocytic Leukemia ◽  
Complex Karyotype ◽  
Event Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Cytogenetic Abnormalities

Background: Current risk stratification for patients with acute promyelocytic leukemia (APL) is based solely on the presenting white blood cell count. There are conflicting data concerning the prognostic relevance of additional cytogenetic abnormalities (ACA) beyond t(15;17) and whether the presence of such abnormalities might influence treatment decisions for patients with APL. This is especially unclear among patients receiving ATO given that many existing data are from patients treated prior to incorporation of ATO into treatment paradigms. We sought to determine the prognostic importance of ACA and complex karyotype (CK) in influencing event-free survival in patients with APL. Methods: We analyzed patients with APL evaluated at our center since 2005 and patients treated in the Australasian Leukaemia and Lymphoma Group APML4 study (frontline ATRA + ATO + idarubicin,Lancet Haematology2015). We included all patients with baseline karyotype and those without karyotype but with FISH at diagnosis revealing ACA. Chart review extracted patient, disease, and clinical data. Only patients who commenced induction therapy with an ATO-based regimen were included in this analysis to ensure uniformity of the study population and applicability of results to contemporary clinical practice in APL. We also included patients deceased early in the disease course (&lt;1 month). We excluded patients with absent follow-up information given our interest in relapse and patients who relapsed prior to transferring care to our center. We defined CK as the presence of &gt;1 ACA beyond t(15;17). Coagulopathy was defined as either APTT/mean laboratory normal APTT &gt;1.5, INR &gt;1.5 (PT/mean laboratory normal PT &gt;1.5 when INR and ISI unavailable), or fibrinogen &lt;100 mg/dL. We defined events as either relapse or death. Associations between time-to event outcomes and patient and disease characteristics were assessed were calculated using univariate Cox proportional hazards models in each study separately. Fixed-effect meta analyses was used to combine estimates from both studies. Results: A total of 168 patients were included (N = 49 MSKCC, 109 APML4); 6 patients were removed from the MSKCC cohort due to relapse prior to initial visit and one from APML4 due to lack of follow-up information (Table 1). The mean age at diagnosis was 47 years in the MSKCC cohort and 43 years in the APML4. Median follow-up among survivors was 36 months (MSKCC, range 2-144) and 54 months (APML4, range 28-96); overall survival is displayed in Figure 1. Forty-nine (31%) patients' disease harbored ACA (most commonly trisomy 8 in 25 patients), and 17 CK (12% MSKCC, 10% APML4, denominator excludes one patient with single ACA by FISH). The event-free survival did not differ between ACA+ and ACA- (Table 2), but patients with +CK harbored inferior EFS (9/139 events non-CK vs. 4/17 events CK). No other clinical parameters that we queried correlated with EFS. Conclusions: In a large cohort pooled from a single-center experience and a cooperative prospective trial, the presence of an ACA beyond t(15;17) did not influence EFS in patients with APL. However, our data suggested that CK influences EFS. Further studies could collect data from other cooperative trials and/or single institutions to garner adequate power to better address the question of CK influencing EFS and confirm these preliminary findings. If a convincing signal emerges, treatment paradigms could be altered in the context of a prospective study (for example, intensifying or prolonging treatment) towards overcoming this adverse effect. Disclosures Park: Minverva:Consultancy;Kite:Consultancy, Research Funding;Amgen:Consultancy, Research Funding;Intellia:Consultancy;Artiva:Membership on an entity's Board of Directors or advisory committees;AstraZeneca:Consultancy;Incyte:Consultancy, Research Funding;GSK:Consultancy;Juno Therapeutics:Research Funding;Autolus:Consultancy, Research Funding;Genentech/Roche:Research Funding;Fate Therapeutics:Research Funding;Servier:Consultancy, Research Funding;Takeda:Consultancy, Research Funding;Novartis:Consultancy;Allogene:Consultancy.Stein:Biotheryx:Consultancy;Bayer:Research Funding;Genentech:Consultancy, Membership on an entity's Board of Directors or advisory committees;Syndax:Consultancy, Research Funding;Seattle Genetics:Consultancy;Abbvie:Consultancy;Amgen:Consultancy;Celgene Pharmaceuticals:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Agios Pharmaceuticals:Consultancy, Membership on an entity's Board of Directors or advisory committees;Astellas Pharmaceuticals:Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;PTC Therapeutics:Membership on an entity's Board of Directors or advisory committees;Syros:Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.Tallman:Bioline rx:Membership on an entity's Board of Directors or advisory committees;Amgen:Research Funding;Rafael:Research Funding;Orsenix:Research Funding;ADC Therapeutics:Research Funding;BioSight:Membership on an entity's Board of Directors or advisory committees, Research Funding;Glycomimetics:Research Funding;Novartis:Membership on an entity's Board of Directors or advisory committees;Roche:Membership on an entity's Board of Directors or advisory committees;UpToDate:Patents & Royalties;KAHR:Membership on an entity's Board of Directors or advisory committees;Rigel:Membership on an entity's Board of Directors or advisory committees;Delta Fly Pharma:Membership on an entity's Board of Directors or advisory committees;Oncolyze:Membership on an entity's Board of Directors or advisory committees;Jazz Pharma:Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo:Membership on an entity's Board of Directors or advisory committees;Cellerant:Research Funding;Abbvie:Research Funding.

scholarly journals A Single-Center Retrospective Cohort Analysis of Venetoclax in Relapsed/Refractory Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5576-5576 ◽  
Author(s):  
Swetha Kambhampati ◽  
Derek Galligan ◽  
Guy Ledergor ◽  
Thomas G. Martin ◽  
Jeffrey Wolf ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Response Rate ◽  
Off Label Use ◽  
Final Dose ◽  
Advisory Committees ◽  
Off Label ◽  
Best Response

Background Despite recent advances, treatment of relapsed refractory multiple myeloma (RRMM) remains a challenge. Venetoclax, a BH3 mimetic, is an oral, specific, and potent small molecule inhibitor of BCL-2 that has been approved for treatment of 17p-deleted CLL and in combination with azacitidine or decitabine in AML patients >/= 75 years of age.Pre-clinical and clinical studies suggest that bcl-2 inhibition can induce MM cell death and may synergize with bortezomib and dexamethasone. Based on this, several prospective clinical trials of venetoclax in RRMM have been performed. However, clinical use of this targeted therapeutic for salvage therapy in RRMM has not been well described. Methods We performed a single-center, retrospective chart review of all patients with RRMM diagnosed after January 1, 2009 who were treated with off-label use of venetoclax. The goal of this study was to describe the clinical characteristics of these patients, assess the response to salvage treatment with venetoclax as determined by the International Myeloma Working Group (IMWG) criteria, and assess the toxicities during salvage treatment with venetoclax in an academic practice setting. Results 43 patients were identified. Median number of lines of prior therapy was 7 (range 2-13). 12 patients had documented high risk cytogenetics, defined as the presence of a 17p deletion, t(14;16), t(14;20), t(4,14), gain (1q), or nonhyperdiploidy. Of the 36 patients with cytogenetics/FISH available, 8 had t(11;14). 34 patients were refractory to bortezomib. 40 patients had progressed after carfilzomib, 36 after pomalidomide, and 41 after anti-CD38 antibody therapy. 39 patients were treated with venetoclax in combination with a proteasome inhibitor (bortezomib (n=36); carfilzomib (n=3)). 23 patients were treated with venetoclax, proteasome inhibitor, and dexamethasone. Patients were started at 400 mg daily for 7 days then increased to the median dose of 800mg daily (11 received < 800mg/daily as a final dose and one received >800 mg/daily as final dose). Overall patients were on treatment for a median of 67 days (range 2-855). 2 patients received intermittent venetoclax therapy, defined as being off venetoclax for at least 3 months before restarting. Best response by IMWG criteria include; CR 5%( 2/43), VGPR 12% (5/43) and PR 16% (7/43) for an overall response rate of 33% (14/43). In addition, MR was seen in 5% (2/43) and stable disease in 9% (4/43). Fifty-one percent (22/43) had progressive disease (PD). Out of the 8 patients who had t(11;14), best responses were: 2 VGPR, 2 PR, 1 SD, and 3 PD for a response rate of 50% (4/8) in this subgroup. Median time to best response for all responding patients was 90 days (range 15-305) and median duration of response was 206 days (range 28-820). At time of data collection, median follow-up time from venetoclax treatment initiation was 192 days (range 8-1058). Four patients have not progressed and remain on therapy, 23 patients remain alive, and 4 patients have been lost to follow-up for over 6 months. The most common treatment related AEs were cytopenias including leukopenia in 26 /43 (60%) patients, neutropenia in 19/43 (44%) patients, and thrombocytopenia in 22/43 (51%) patients. Non-hematologic toxicities included diarrhea in 12/43 (30%) patients, nausea/vomiting in 15/43 (35%) patients, infections in 11/43 (26%) patients, and fatigue in 23/43 (53%) patients. 8/43 (19%) patients required dose reduction, 7/43 (16%) patients required temporary discontinuation of treatment, and 4/43 (9%) patients required permanent discontinuation due to treatment related AEs. 38/43 (88%) patients had any grade treatment related AEs, 27/43 (63%) patients had grade >/= 3 AEs and 2/43 (5%) patients had treatment related SAEs. One patient had a treatment related death from an infectious complication (CMV pneumonitis). Conclusions Venetoclax is an active and well-tolerated agent in relapsed multiple myeloma. Furthermore, it is easily administered in the outpatient setting. Additional areas of research with this therapy include understanding the importance of t(11:14) for response and selecting the best anti-MM partner for combination therapy. Disclosures Ledergor: Venetoclax: Other: off-label use; Immunai: Consultancy. Martin:Roche and Juno: Consultancy; Amgen, Sanofi, Seattle Genetics: Research Funding. Wolf:Takeda: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Amgen: Consultancy. Wong:Celgene Corporation: Research Funding; Genentech: Research Funding; Janssen: Research Funding; Fortis: Research Funding; Juno: Research Funding. Shah:Nkarta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene, Janssen, Bluebird Bio, Sutro Biopharma: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Poseida: Research Funding; Genentech, Seattle Genetics, Oncopeptides, Karoypharm, Surface Oncology, Precision biosciences GSK, Nektar, Amgen, Indapta Therapeutics, Sanofi: Membership on an entity's Board of Directors or advisory committees; University of California, San Francisco: Employment; Indapta Therapeutics: Equity Ownership; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teneobio: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: This study is looking at the safety and efficacy of venetoclax in relapsed refractory myeloma patients who are treated off-label since venetoclax is not currently approved for multiple myeloma

scholarly journals Spirit 2: An NCRI Randomised Study Comparing Dasatinib with Imatinib in Patients with Newly Diagnosed CML

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 517-517 ◽  
Author(s):  
Stephen G O'Brien ◽  
Corinne Hedgley ◽  
Sarah Adams ◽  
Letizia Foroni ◽  
Jane F. Apperley ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Blast Crisis ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Event Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
The Difference

Abstract Objective. SPIRIT 2 is the largest phase 3 prospective randomized open-label trial comparing imatinib 400mg with dasatinib 100mg daily: this is the first presentation of data comparing the two arms. Methods. 814 patients were recruited at 144 hospitals between August 2008 and March 2013. 812 started study medication (406 in each arm). The primary endpoint is event-free survival at 5 years. A key secondary endpoint is the rate of achievement of a BCR-ABL/ABL ratio of &lt;0.1%IS (major molecular response (MMR), 3 log reduction or MR3). Results. Discontinuations. With a median follow up of 34 months a total of 289/812 (35.6%) patients have discontinued study medication. 118/812 (14.5%) patients have discontinued due to non-haematological toxicity: imatinib 47/406 (11.6%); dasatinib 71/406 (17.5%). 40 patients discontinued due to sub optimal response as assessed by the treating physician: imatinib 37/406 (9.1%); dasatinib 3/406 (0.7%). Side effects. Patients receiving imatinib experienced GI toxicity more often than patients receiving dasatinib; fatigue, rash and headache were more common with dasatinib. A higher rate of grade 3/4 thrombocytopenia was observed in the dasatinib arm: imatinib 17/406 (4.2%); dasatinib 52/406 (12.8%). Pleural effusions occurred in 78/406 (19.2%) patients on dasatinib; 13 of 78 (16.7%) patients required drainage. Arterial cardiovascular events (excluding hypertension) were experienced by 10/812 (1.2%) patients: imatinib 2/406 (0.5%; myocardial infarction (MI) x2); dasatinib 8/406 (2.0%; MI x1; angina/acute coronary syndrome x5; peripheral arterial disease x2). Hypertension was observed in 10/812 (1.2%) patients: imatinib 3/406 (0.7%); dasatinib 7/406 (1.7%). Venous CV events occurred in 7/812 (0.9%) patients: imatinib 3/406 (0.7%); dasatinib 4/406 (1.0%).Efficacy.For both PCR and cytogenetic analyses patients that had discontinued their allocated therapy or that did not have a 12 month sample were analysed as not having achieved MR3/CCR. The MR3 (PCR &lt;0.1% IS) rate at 12 months in all treated patients is significantly different (p&lt;0.001) between the two treatment arms: imatinib 173/406 (42.6%); dasatinib 236/406 (58.1%). The MR3 rate at 12 months in patients treated with dasatinib is 51/78 (65.4%) in those with a pleural effusion and 185/328 (56.4%) in those without (p=0.148, NS).The complete cytogenetic response (CCR) rate at 12 months is: imatinib 163/406 (40.1%); dasatinib 207/406 (51.0%). The difference between the two treatment arms is statistically significant (p=0.002) but caution is required in interpreting these data as there were missing analyses in 367 of 812 (45.2%) patients: imatinib 191 of 406 (47.0%), dasatinib 176 of 406 (43.3%). The difference in major cytogenetic response (MCR) rate between the two treatment arms at 12 months is not statistically significant: imatinib 200/406 (49.3%); dasatinib 218/406 (53.7%), p=0.206.Disease progression and deaths. 16 patients have progressed to either accelerated phase or blast crisis and 13 of those progressions were within the first year. Accelerated phase: imatinib 3/406 (0.7%); dasatinib 2/406 (0.5%). Blast crisis: imatinib 7/406 (1.7%); dasatinib 4/406 (1.0%). Conclusions. Dasatinib-treated patients have a higher rate of molecular response at 1 year but, with a median of 34 months follow up, there is no significant difference in rates of disease progression or overall survival. More patients abandoned imatinib than dasatinib due to investigator concerns about sub optimal responses. Further follow up is required to evaluate whether there will be differences in event free survival at five years. Disclosures O'Brien: Ariad: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding. Hedgley:BMS: Research Funding; ARIAD: Research Funding. Adams:BMS: Research Funding. Apperley:Ariad Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Holyoake:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees. Byrne:BMS: Honoraria; Novartis: Honoraria; Pfizer: Consultancy, Honoraria; Ariad: Consultancy. Osborne:ARIAD: Research Funding. Copland:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Ariad: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria. Clark:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi-Aventis: Honoraria, Research Funding.

Autologous Stem Cell Transplantation (ASCT) Versus Oral Melphalan and High-Dose Dexamethasone In Patients with AL (Primary) Amyloidosis: Long Term Follow-up of the French Multicentric Randomized Trial

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1344-1344 ◽  
Author(s):  
Arnaud Jaccard ◽  
Veronique Leblond ◽  
Bruno Royer ◽  
Xavier Leleu ◽  
Richard Delarue ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Median Survival ◽  
Research Funding ◽  
High Dose ◽  
Event Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Landmark Analysis ◽  
To Receive

Abstract Abstract 1344 In September 2007 we published the results of a prospective randomized trial comparing in 100 AL amyloidosis patients, enrolled between January 2000 and January 2005, high dose melphalan with ASCT and the oral regimen M-Dex (melphalan 10 mg per square meter of body-surface area and dexamethasone 40 mg per day, on days 1 to 4). With a median follow-up of 3 years the median survival was better in the M-Dex arm (56.9 months) than in the ASCT arm (22.2) months (p=0.04). The hematological responses were not statistically different between the 2 arms and the higher toxicity of the ASCT arm was responsible for the shorter median survival. This study has been criticised because of the high treatment related mortality (TRM) in the ASCT arm but a landmark analysis of patients who survived for at least 6 months and who received their assigned treatment, did not show any difference in survival. A second frequent criticism was that too severe patients, who were not able to go through the high dose procedure, have been included. A separate analysis done within the 59 good risk patients showed a nonsignificant difference between the two groups in overall survival at 3 years (58% in the group assigned to receive ASCT vs. 80% in the group assigned to receive M-Dex; P = 0.13). A third concern was related to the duration of response, should high dose treatment, giving slightly more complete responses, results in more sustained responses and, with a prolonged follow-up, in a better long term survival ? To answer this question we extended the follow-up of the surviving patients. The new cut off date was August 1st, 2010, more than 5 and a half years after the last inclusion. Only 1 patient has been lost to follow-up. We did again the landmark analysis with the longer follow-up and we looked, in this population of 65 patients with 100% feasibility and 0 % TRM, at survival and remission duration. As the follow-up was very long and the biologic surveillance not planned after 2006 we took unequivocal events as censor points for the event-free survival analysis: deaths and second line treatment. At the first cutoff date, in 2006, 49 patients were alive, 30 in the M-Dex arm and 19 in the HDT arm. At the new cutoff date in 2010, 38 patients are alive, 22 in the M-Dex arm and 16 in the intensive arm, with a median follow-up of 49 months for the entire cohort and 86 months for surviving patients (figure 1). The majority of late deaths were amyloid related, but 3 patients in the M-Dex arm died of unrelated lung and digestive cancer. The median survival in the 2 arms has not been modified (56.9 month in the M-Dex arm and 22.2 month in ASCT arm, p=0.15). For the 65 patients included in the landmark analysis the median survival is not different in the 2 arms (103 month in the M-Dex arm and 97 month in ASCT arm) and the median event free survival is 56 months in the M-Dex arm and 26 months in the intensive arm (p=0.3, figure 2). Eleven surviving patients in the M-Dex arm and 6 in the intensive have not received a second treatment, 9 of these patients in the M-Dex arm and 5 in the ASCT arm have normal free light chain measurement at their last visit. Only 1 patient, assigned to receive ASCT, has been diagnosed with myelodysplasia. With a longer follow-up we did not found any superiority in the intensive arm in survival or remission duration even in the landmark analysis eliminating treatment related mortality. In the area of very efficient new drugs this analysis reinforces our choice to propose conventional treatment to amyloidosis patient avoiding the risk of intensive treatment.Figure 1.Survival according to treatment groupFigure 1. Survival according to treatment groupFigure 2.Event-Free Survival According to Treatment Group in the Landmark AnalysisFigure 2. Event-Free Survival According to Treatment Group in the Landmark Analysis Disclosures: Leblond: roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; mundipharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; genzyme: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees. Leleu:Celgene: Consultancy, Research Funding; Janssen Cilag: Consultancy, Research Funding; Leo Pharma: Consultancy; Amgen: Consultancy; Chugai: Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

scholarly journals Radioimmunotherapy for Mantle Cell Lymphoma: 5-Year Follow-up of 90 Patients from the International RIT-Registry

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5263-5263
Author(s):  
Karin Hohloch ◽  
Christine Windemuth-Kieselbach ◽  
Pier Luigi Zinzani ◽  
Roberto E. Cacchione ◽  
Wojciech Jurczak ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Mantle Cell Lymphoma ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Primary Therapy ◽  
First Line ◽  
Advisory Committees ◽  
Mantle Cell

To assess the efficacy of radioimmunotherapy (RIT) with 90yttrium-ibrutinib-tiuxetan (90Y-IT) in mantle cell lymphoma, data from 90 patients registered in the RIT Network with a median follow-up (FU) of 5.5 years after RIT were evaluated. 90Y-IT was given as first-line therapy in 45 (50%) (consolidation 44 pts., primary therapy 1 pt.) and at relapse in 45 (50%) patients (consolidation 24 pts., recurrence 12 pts., therapy refractory 3 pts., conditioning 2 pts., other 4 pts.). As a first-line treatment, 30 patients (pts.) (67%) achieved CR, 10 pts. (22%) PR%., 1 pt. (2%) PD, and for 4 pts. (9%) no response data was available. At relapse, CR was achieved in 17 pts. (38%), PR in 6 pts. (13%), SD in 2 pts. (4%), and 6 pts. (13%) had PD, while the response was not documented for 14 pts. (31%). After a median FU of 5.5 years, median PFS for all patients was 2.11 (95%CI: 1.03-2.32) years, and median OS was 4.05 (95%CI 2.79-7.21) years. Eleven pts. (12.2%) developed second malignancy. In conclusion, this is the largest report of MCL pts. treated with 90Y-IT to date. 90Y-IT was most often used as consolidation after first- and second-line chemotherapy and may improve the results achieved using chemoimmunotherapy alone. However, the results are less encouraging compared to treatment with small molecules such as ibrutinib. Disclosures Zinzani: TG Therapeutics: Honoraria, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy. Jurczak:Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Roche: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bayer: Research Funding; Gilead: Research Funding; MorphoSys: Research Funding; Incyte: Research Funding; Novo Nordisk: Research Funding; Servier: Research Funding; TG Therapeutics: Research Funding; Celtrion: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Truemper:Seattle Genetics, Inc.: Research Funding; Takeda: Consultancy, Research Funding; Roche: Research Funding; Nordic Nanovector: Consultancy; Mundipharma: Research Funding; Janssen Oncology: Consultancy. Scholz:Janssen-Cilag: Consultancy; Hexal: Consultancy; Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Pfizer: Speakers Bureau; Roche: Consultancy; GILEAD: Consultancy, Speakers Bureau; Daiichi Sankio: Consultancy. OffLabel Disclosure: Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin) is approved for treatment of patients with relapsed follicular lymphoma and as consolidation therapy after chemo(immuno)therapy of patients with follicular lymphoma.

scholarly journals Ponatinib and Chemotherapy in Young Adults with De Novo Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Results of Ponalfil Clinical Trial after Completion of Recruitment

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Josep-Maria Ribera ◽  
Olga García ◽  
Pau Montesinos ◽  
Pilar Martinez ◽  
Jordi Esteve ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Molecular Response ◽  
Event Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Allogeneic Hsct ◽  
Central Artery

Background and objective. The combination of tyrosine kinase inhibitors (TKI) and chemotherapy (intensive, attenuated or minimal) has improved the prognosis of patients (pts) with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). The combination of HyperCVAD and ponatinib has improved the molecular response and survival compared with other combinations of chemotherapy with first or second generation TKI (Jabbour E, et al, Lancet Haematol. 2018; 5:e618-e627). The Spanish PETHEMA group conducted the phase 2 PONALFIL trial, which incorporates ponatinib to the same induction and consolidation schedule of the ALL Ph08 trial (Ribera JM et al. Cancer 2019;125:2810-2817) The results of this trial after completed recruitment are herein reported. Patients and method. The PONALFIL trial (NCT02776605) combined ponatinib (30 mg/d) and induction chemotherapy (vincristine, daunorubicin and prednisone) followed by consolidation (high-dose methotrexate, ARA-C, mercaptopurine, etoposide) and allogeneic HSCT. TKI use as maintenance was only scheduled for pts with persistence or reappearance of MRD. By July 2020 the 30 scheduled pts were recruited. The response to therapy (complete morphological [CR], molecular [complete, CMR or major, MMR] after induction and before allogeneic HSCT) (assessed by centralized BCR-ABL/ABL ratio),event-free survival (EFS), overall survival [OS]) and toxicity are herein analyzed. Results. Median age was 50 (20-59) years and 14/30 pts were female. One pt showed CNS involvement at diagnosis. ECOG score at diagnosis was &lt;2 in 86% of pts. Median of WBC count was 6.4 (0.6-359.3) x109/L, Hb 90 (63-145) g/L, platelets 38 (11-206) x109/L. The immunologic phenotype was common in 26 cases, with molecular isoform p190 in 20 patients (67%), p210 in 9 (30%) and p230 in 1 (3%). CR was attained 26/26 patients (100%) (4 are still on induction therapy), with CMR in 11/26 cases (42%), MMR in 6/26 (23%) and no molecular response in 9/26 (35%)).Two patients withdrew the trial (thrombosis of the central retina artery and severe intestinal infection, one case each). Consolidation was given to 24 patients, 2/24 are receiving consolidation and 22 patients received allogeneic HSCT (14 in CMR, 6 in MMR, 2 without molecular response). No relapses before HSCT were detected. No transplant-related mortality was observed to date, but 1 patient withdrew the trial by severe GVHD. Ponatinib was given after HSCT in 4 pts due to loss of molecular response. Three pts relapsed after HSCT, one of them after documented loss of molecular response. All pts are alive (median follow-up of 4.5 months, range 0.5-26.2.2). The EFS probability at 30 months was 91% (79%, 100%) (Figure 1). One hundred and two adverse events (AE) have been registered in 20 patients, 25 of whom were severe (SAE) and occurred in 14 patients, prompting to withdrawn of the trial in 3 (thrombosis of the central artery of the retina, severe bowel infection, grade IV aGVHD, one case each). The most frequent AE were hematologic (26%), gastrointestinal (15%), infections (10%), hepatic (8%) and cutaneous (5%). Cardiovascular events occurred in 2 patients (angor pectoris and thrombosis of central artery of the retina, one case each). Conclusions. The preliminary results of the PONALFIL trial after recruitment completed show a high short-term antileukemic efficacy with acceptable toxicity profile. Supported in part by grant 2017 SGR288 (GRC) Generalitat de Catalunya and "La Caixa" Foundation. Figure 1. Event free survival (EFS) of the whole series. Figure 1 Disclosures Ribera: Pfizer, Amgen, Ariad, Novartis: Consultancy, Speakers Bureau; Pfizer, Amgen: Research Funding. Martinez-Lopez:Incyte: Consultancy, Research Funding; Novartis: Consultancy; BMS: Consultancy, Research Funding; Janssen-cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria. Garcia-Sanz:Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Gilead: Honoraria, Research Funding; Incyte: Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria; Pharmacyclics: Honoraria; Takeda: Consultancy, Research Funding.

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