ABVD Chemotherapy Results in Excellent Outcomes with Reduced Radiation Therapy Rates in Children, Adolescents and Young Adults with Hodgkin Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2695-2695
Author(s):  
Kristin C. Marr ◽  
Joseph M. Connors ◽  
Karen J. Goddard ◽  
Kerry J. Savage ◽  
Rebecca J. Deyell
Keyword(s):  
Overall Survival ◽  
Young Adults ◽  
Radiation Therapy ◽  
Research Funding ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
Free Survival ◽  
Limited Stage ◽  
Stage Disease

Abstract BACKGROUND Hodgkin lymphoma (HL) incidence peaks in adolescence and young adulthood. The care of patients in this age range must address unique challenges as it spans the transition from pediatric to adult centers and treatment approaches vary considerably. The current standard of care for treatment of HL in adults is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with varying use of consolidation radiation therapy (RT). Multiple large trials in adults have demonstrated excellent long-term survival outcomes for both limited and advanced stage disease, with low rates of long-term toxicity. In British Columbia, Canada, ABVD was adopted for primary treatment of HL in the pediatric population in 2004. Pediatric, adolescent and young adult outcomes following this approach, in combination with reduced rates of RT, have not been reported. We report outcomes of a population-based cohort of children (age <18y) and young adults (18-25y at diagnosis) with HL who received a standardized ABVD regimen across adult and pediatric centers. PATIENTS AND METHODS The study cohort included 222 patients (n=58 < 18y; n=164 18-25y) with all histological subtypes of HL diagnosed from January 1, 2004 to July 1, 2013 who received ABVD as initial therapy. 87 patients had limited stage (IA, IB, IIA, bulk < 10 cm) and 135 had advanced stage disease (IA-IIA with bulk >10 cm and IIB-IVB). Limited stage patients received 2 cycles of ABVD followed by PET/CT assessment. Consolidation treatment consisted of involved-field radiation therapy (IFRT) to the area of original disease for incomplete responders (PET positive) or 2 further cycles of ABVD. Advanced stage patients were treated with 6 cycles of ABVD followed by repeat imaging. IFRT to areas of residual disease (PET positive and/or persistent mass by CT scan) was recommended for those patients with incomplete response. RESULTS There were no significant differences in gender, histology, B symptoms or bulk between children (< 18y) and young adults (18-25y). The pediatric group had higher proportions of Ann Arbor stage III or IV disease (p =.002), possibly related to more frequent use of PET/CT scanning for staging (66% vs 10%, respectively, p= <.001), but the groups were similar following risk stratification into limited (36% vs 40%, respectively) and advanced (64% vs 60%, respectively) stage disease (p =.588). The median follow-up was 64 months. More young adults achieved complete response at end of therapy (95% vs 83%; p =.004). Children were more likely to have primary progressive disease with 9 of 11 treatment failures (82%) occurring during treatment or within 6 months of completion. Patients aged 18-25y were more likely to have late treatment failures, with 41% of relapses occurring greater than 12 months after therapy completion (p =0.014). There were no toxicity-related deaths. The 5 year overall survival (OS) and progression-free survival (PFS) for the entire cohort (n=222) were 97±1% and 84±3%, respectively. In limited stage disease, OS and PFS were 100% and 91±3%, while those with advanced stage had an OS of 95±2 % and PFS of 80±4%. There was no difference in OS (93±4% vs 98±1%, p =.120) or PFS (81±5% vs 85±3%, p =.222) between children and young adults. The rate of consolidative RT was 20% overall (24% in limited stage; 18% in advanced stage) with no difference between age groups (p =.295). CONCLUSION ABVD is an effective treatment for HL in the pediatric, adolescent and young adult populations. Radiation therapy can be omitted for the 75% of patients who achieve a complete response to chemotherapy while maintaining comparable 5 year overall survival outcomes, thus limiting the risk of radiation related long-term toxicities. Figure 1. Overall Survival and Progression-Free Survival for Whole Cohort Figure 1. Overall Survival and Progression-Free Survival for Whole Cohort Figure 2. Overall Survival and Progression-Free Survival by Risk Group and Age Group Figure 2. Overall Survival and Progression-Free Survival by Risk Group and Age Group Disclosures Connors: Roche: Research Funding; Seattle Genetics: Research Funding. Savage:Seattle Genetics: Honoraria, Speakers Bureau; BMS: Honoraria; Infinity: Honoraria; Roche: Other: Institutional research funding.

Should Albumin Be Considered a Prognostic Factor For Brazilian Patients Diagnosed With Classical Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5049-5049
Author(s):  
Guilherme Fleury Perini ◽  
Egyla M Cavalcante ◽  
Joao Garibaldi Rezende ◽  
Davimar Miranda Borducchi ◽  
Fernanda Cunha Vieira ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Partial Response ◽  
Early Stage ◽  
Progression Free Survival ◽  
Refractory Disease ◽  
Advanced Stage ◽  
Classical Hodgkin Lymphoma ◽  
Free Survival ◽  
Stage Disease

Abstract Introduction In 1998, Hasenclever et al published the International Prognostic Factor for patients with advanced stage classical Hodgkin lymphoma (cHL). Since then, the IPS has been considered the most important prognostic score for cHL and has been validated in different populations, and also in early stage cHL. From the seven factors analyzed in the IPS, albumin is the only that can be influenced by environmental, economic and nutritional status. We hypothesized if, in developing countries, albumin should still be a prognostic factor, and if so, what is the ideal cutoff value. Objectives To assess if albumin at diagnosis of cHL patients in Brazil was prognostic for overall survival (OS) and progression free survival (PFS) and what would be the best cutoff. Patient and Methods This is a retrospective multicenter study conducted by the Universidade Federal de São Paulo, São Paulo, Brazil. Only confirmed cases of cHL, diagnosed between April 1996 To January 2013, with clinical, epidemiological and laboratorial parameters available after a thorough chart review were included in this study. Response was defined as complete (CR) or less than CR (partial response or refractory disease). Event was defined as treatment related mortality, progression (defined as time for initiation of salvage therapy) or relapse. Advanced stage disease was defined as stage I or II with B symptoms and/or bulky disease and stage III or IV. Patients with conflicted data or loss of follow up were excluded from the analysis. Results A total of 179 patients were selected for this study. Nodular sclerosis subtype was diagnosed in 125 (68.9%) of all patients. Median age at diagnosis was 28 years old (ranging from 13-76). Only 22.9% of patients presented with early stage disease. ABVD chemotherapy protocol was the initial therapy in 91% of patients. Consolidation radiotherapy was done in 48.6%. Median serum albumin was 3.74 (range: 1.34 – 5.52). Median albumin for patients treated in private hospital was 3.6 (range: 2.7 – 4.7) in contrast to patients treated in public hospitals with a median level of 3.0 (range: 1.34 – 5.52), although this difference was not statistically different. Overall responses were: CR in 90%, Partial response/Refractory disease in 10%; one patient died due to treatment-related toxicity. Overall Survival (OS) for the entire group was 93% in 5 years (CI95% 87-96%), with a progression free survival (PFS) of 79% (CI95% 73-86%). When applying the cutoff of 4g/dL, albumin was not related to OS (91% vs 98%, p=ns) or PFS (85 vs 77%, p=ns). However, an albumin value greater than 2g/dL was related to a better OS (94% vs 71%, p=0.01). Conclusions Prognostic factors may differ from different studied populations. This is particularly truth for albumin, which is the only IPS factor influenced by the environment. In our study, however, albumin was not significantly related to OS or PFS, unless when a cutoff of 2g/dL was used. Disclosures: No relevant conflicts of interest to declare.

Long-term outcomes for low-grade intracranial ganglioglioma: 30-year experience from the Mayo Clinic

2012 ◽  
Vol 117 (5) ◽  
pp. 825-830 ◽  
Author(s):  
Julia J. Compton ◽  
Nadia N. Issa Laack ◽  
Laurence J. Eckel ◽  
David A. Schomas ◽  
Caterina Giannini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Mayo Clinic ◽  
Progression Free Survival ◽  
Low Grade ◽  
Term Survival ◽  
Free Survival

Object Gangliogliomas comprise less than 1% of all brain tumors and occur most often in children. Therefore, there are a limited number of patients and data involving the use or role of adjuvant therapy after subtotal resections (STRs) of gangliogliomas. The objective of this study was to examine and review the Mayo Clinic experience of 88 patients with gangliogliomas, their follow-up, risk of recurrence, and the role of radiation therapy after STR or only biopsy. Methods Eighty-eight patients with gangliogliomas diagnosed between 1970 and 2007 were reviewed. Data on clinical outcomes and therapy received were analyzed. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival. Results The median age at diagnosis was 19 years. The median potential follow-up as of June 2008 was 142 months (range 9–416 months). Fifteen-year overall survival was 94%, median PFS was 5.6 years, with a 10-year PFS rate of 37%. Progression-free survival was dramatically affected by extent of initial resection (p < 0.0001). Conclusions This single-institution retrospective series of patients with gangliogliomas is unique given its large cohort size with a long follow-up duration, and confirms the excellent long-term survival rate in this group. The study also shows the importance of resection extent on likelihood of recurrence. Patients with gangliogliomas who undergo STR or biopsy alone have poor PFS. Radiation therapy may delay time to progression in patients with unresectable disease.

Early Consolidation with Myeloablative Radiochemotherapy Followed by Autologous Stem Cell Transplantation in First Remission Significantly Prolongs Progression-Free Survival in Mantle Cell Lymphoma - Long Term Follow up of a Prospective Randomized Trial of the European MCL Network.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 7-7 ◽  
Author(s):  
Martin H. Dreyling ◽  
Georg Lenz ◽  
Eva Schiegnitz ◽  
Achiel van Hoof ◽  
Christian Gisselbrecht ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
Free Survival ◽  
Mantle Cell ◽  
First Remission

Abstract Mantle cell lymphoma (MCL) is a distinct subtype of malignant lymphoma with an especially poor prognosis and a median survival of only 3–4 years. In 1996, the European MCL Network initiated a randomized trial to improve the otherwise dismal outcome of MCL, comparing early consolidation with myeloablative radiochemotherapy (TBI 12 gray, cyclophosphamide 120 mg/kg bw) followed by autologous stem cell transplantation (ASCT) to a conventional a -interferon maintenance (6x106 IE IFNa 3x weekly) in first remission after a CHOP-like induction regimen. Until March 2004, a total of 269 previously untreated patients (up to 65 years) were randomized upfront. 189 (82%) of 230 patients with advanced stage MCL completed initial induction chemotherapy and 142 (75%) achieved either a complete (45 pts., 24%) or partial response (97 pts, 51%). 122 pts proceeded to consolidation therapy, 62 pts received ASCT consolidation and 60 patients were assigned to IFN maintenance. Patients in the ASCT study arm experienced a significantly longer progression-free survival (PFS) as compared to patients in the IFNa arm. The PFS at 2 years was 73% after ASCT as compared to only 43% in the IFNa arm (p = 0.0108). Similar results were achieved in the intent to treat analysis of all initially randomised MCL patients (p=0.0001). Accordingly, this advantage resulted in a trend towards an improved overall survival (OS) in the ASCT arm. After a follow-up of up to nearly 7 years (median follow-up of patients: 2.8 years), 3 year survival after ASCT was 83% in comparison to 77% under IFNa maintenance (p = 0.18). As expected, acute toxicity was higher in the ASCT group with an early mortality of 4.8%, whereas long-term effects were more frequently encountered under IFNa maintenance. Conclusion : In first line treatment of advanced stage MCL, dose-intensified consolidation with myeloablative radiochemotherapy followed by ASCT after CHOP-like induction results in a significant prolongation of PFS. Current study concepts evaluate the benefits of combined immuno-chemotherapy to further improve the overall survival.

Sequential RCHOP, Radioimmunotherapy and Rituximab Maintenance Improves Early Outcomes in Advanced Stage Follicular Lymphoma: 5 Year Outcomes from SWOG 0801

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 614-614
Author(s):  
Paul M. Barr ◽  
Hongli Li ◽  
Richard Burack ◽  
Michael LeBlanc ◽  
Sonali M. Smith ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Research Funding ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
Secondary Malignancies ◽  
Free Survival ◽  
Grade 3

Abstract Background: Despite an abundance of effective therapeutic options, advanced stage follicular lymphoma (FL) remains incurable. Further, prospective trials consistently demonstrate that 20% of patients relapse within 2 years and ultimately have an inferior survival (Casulo 2015). Maintenace rituximab following chemoimmunotherapy induction is able to delay disease progression but has not demonstrated a benefit in overall survival (Salles 2011). Additionally, radioimmunotherapy (RIT) is one of the most effective single agent options in FL but is not commonly utilized as part of upfront treatment. As such, the role of both remains unclear. Based on results demonstrated with RIT consolidation in SWOG 0016 and the efficacy of rituximab maintenance, SWOG 0801 was designed as a phase 2 single arm trial, conducted to evaluate the utility of consolidative RIT and sequential maintenance rituximab following chemoimmunotherapy induction. Methods: Eligible patients (pts) with treatment naïve stage III/IV or bulky stage II FL received RCHOP for 6 cycles (without rituximab for the last 2 cycles) followed by iodine-131 tositumomab and subsequent rituximab administered every 3 months for up to 4 years. The primary endpoint was progression-free survival (PFS) at 3 years. Secondary endpoints included 5-year overall survival (OS), overall response rate (ORR), and safety. Results: Of 87 pts registered to this study, 85 were deemed eligible following central pathologic review. One additional patient withdrew consent and received no treatment on protocol. Of the 84 evaluable patients, the median age was 52 years (range 29 - 80) ) and 18%, 40%, and 42%had low, intermediate and high risk FLIPI scores, respectively. Seventy-three pts completed RCHOP and I-131 tositumomab. Grade ≥3 AEs occurring ≥5% of pts included neutropenia (57%), leukopenia (40%), thrombocytopenia (20%), febrile neutropenia (17%), fatigue (10%), neuropathy (8%), anemia (7%) and hyperglycemia (5%). Reasons for discontinuation included refusal of tositumumab (6 pts), prolonged myelosuppression (2 pts), ascites (1pt), inability to provide tositumumab (1 pt), and an unrelated lower extremity wound (1 pt). Following induction and RIT, 59 complete responses and 23 partial responses were observed, for a ORR of 99% (95% CI: 93.5%, 99.9%) Sixty nine eligible patients registered to maintenance therapy with 42 completing the 4 year treatment plan. The only grade ≥3 AE that occurred in ≥5% of pts was leukopenia (5%). Twenty-seven pts discontinued maintenance therapy, including 11 in the first 2 years and 16 in the last 2 years, due to the following reasons: infection (8 pts), patient preference (8 pts), deaths (2 pts), treatment delay (2 pts), secondary solid tumors (2 pts), bowel perforation (1 pt), joint pain (1 pt), hepatic transaminase elevation (1 pt), insurance refusal (1 pt), and dose error (1 pt). Four additional secondary malignancies were reported following completion of therapy including solid tumors (3 pts) and AML (1 pt). To date, 9 deaths have occurred due to secondary malignancies (3 pts), unknown etiology (3 pts), cardiac arrest (2 pts) and non-alcoholic cirrhosis (1 pt). After median follow-up of 5.6 years (range 3-7 years), 17 events have occurred including 9 pts experiencing progressive FL resulting in a progression free survival of 90% (95% CI: 81.9%, 95.1%) at 3 years and 84%(95% CI: 74.5%, 90.6%) at 5 years (Figure). Three-year overall survival is 96% (95% CI: 89.3%, 98.8%) and 5-year overall survival is 94% (95% CI: 86.2%, 97.5%). Conclusions: SWOG 0801 demonstrates near universal responses following chemoimmunotherapy and RIT. This sequential therapeutic strategy appears to improve early outcomes as 94% of pts are without disease progression at 2 years, consistent with the best results ever demonstrated for FL in the National Clinical Trials Network. However, the majority of discontinuations occurred during maintenance suggesting that rituximab over a 4-year span is not feasible for many patients due to cumulative toxicity. Future studies investigating precision strategies in high-risk FL may consider an aggressive chemoimmunotherapy induction and RIT consolidation platform to overcome early FL progression given these promising outcomes. Support: NIH/NCI grants CA180888, CA180819, and in part by GlaxoSmithKline. Figure. Progression-Free Survival and Overall Survival Figure. Progression-Free Survival and Overall Survival Disclosures Barr: Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy. Smith:Amgen: Other: Educational lecture to sales force; Juno: Consultancy; Pharmacyclics: Consultancy; AbbVie: Consultancy; Portola: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Genentech: Consultancy, Other: on a DSMB for two trials ; TGTX: Consultancy. Gopal:Janssen: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Spectrum: Consultancy. Persky:Merck: Research Funding; Gilead: Speakers Bureau. Press:Roche / Genentech: Consultancy, Research Funding. Fisher:Gilead: Consultancy; Seattle Genetics: Consultancy; Johnson and Johnson: Consultancy. Friedberg:Bayer: Other: Data Safety Monitoring Committee.

scholarly journals Outcomes in Advanced-Stage Plasmablastic Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2519-2519
Author(s):  
Sophia Lee ◽  
Christen Dillard ◽  
Raphael E Steiner ◽  
Babak Soltanalizadeh ◽  
Lei Feng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Research Funding ◽  
Progression Free Survival ◽  
Plasmablastic Lymphoma ◽  
Advanced Stage ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction: Plasmablastic lymphoma (PBL) is a rare subtype of non-Hodgkin B-cell lymphoma (NHL), often characterized by immunoblastic morphology and plasmacytic immunophenotype. PBL was initially described in HIV-positive patients (pts) and is now often diagnosed in post-transplant and HIV-negative pts with other immunodeficiency. Pts with limited stage disease treated with induction chemotherapy and consolidative radiotherapy have a good prognosis; however, pts with advanced stage have poor outcome. Previously studied treatment regimens vary and include CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone), HyperCVAD (cyclophosphamide, vincristine, Adriamycin, dexamethasone alternating with methotrexate and cytarabine), and DA-EPOCH (etoposide, vincristine, cyclophosphamide, Adriamycin, prednisone) with or without radiation and autologous stem cell transplant, with no current standard therapy, largely due to the rarity of PBL. Methods: We conducted a retrospective analysis of pts diagnosed with PBL between April 2003 and August 2020 to describe outcomes for pts treated at our center over the past 2 decades. We hope to use this to improve outcomes with novel therapies in the future. We evaluated the baseline demographics, stage, therapy, response rate, progression-free survival (PFS) and overall survival (OS). We used descriptive statistics including mean, standard deviation, median, and range for continuous variables, and frequency counts and percentages for categorical variables. Best response and its 95% exact confidence interval were calculated. Kaplan-Meier method was used to estimate the time-to-event endpoints including progression free survival, and overall survival. Results: 39 pts with PBL were identified, with a median age of 51 years (range 27-91). 16 were HIV+, and 5 were on immunosuppression for autoimmune disease (2), infectious hepatitis (2), or liver transplant (1); the other 18 had no apparent immunosuppression other than advanced age (defined as 70 years and older) in 13. Among those with HIV, 14 were on antiretroviral therapy at time of diagnosis of PBL. The median CD4 count was 140 (range 15-391) and 5 patients had an active viral load. 24 pts were EBV/EBER positive. 6 pts had stage III disease and 33 had stage IV disease. The primary sites of disease included head and neck (13), lymph node (7), gastrointestinal tract (6), other soft tissue (3), abdomen (3), breast (2), gynecologic (2), skin (2), and bone (1). The median LDH was 629 IU/L (313-618). A serum protein electrophoresis was checked in 21 pts and the median was 1.4 g/dL (range 0.2-2.6 g/dL, normal = 0). A beta 2 microglobulin was checked in 28 pts and the median was 3.95 (range 2.55-10.4, normal =0.8 to 2.3 mg/L). The median Ki-67 proliferation index was 85%, and the PBL cells were invariably CD20 negative. 12 cases showed MYC overexpression; 2 had MYC rearrangement by FISH. 32 pts received systemic therapy and were evaluable with 2 median lines of treatment (range 1-6). First line therapy included Hyper-CVAD (n=7), CHOP (n=3), EPOCH (n=19), and other (n=3). The antimyeloma therapy, bortezomib, a proteasome inhibitor, was added to EPOCH for 4 patients or used with dexamethasone in one pt, while the CD38 antibody daratumumab was added to hypercytoxan for the first cycle of an elderly pt with poor performance status (PS). He responded well with improvement in his PS, and subsequently completed 5 cycles of DA-EPOCH and remains in CR. After first line therapy, 59% pts achieved complete response, 13% partial response, and 9% stable disease. 20 pts received intrathecal chemotherapy, 9 pts received radiation, and 8 pts underwent autologous stem cell transplantation (7 as consolidation and 1 at relapse). Please see figure for PFS and OS based on different treatment modalities. Median PFS and OS were 21 and 35.2 months, respectively. Median follow up time was 25.85 months. Conclusions: The majority of our pts (87%) with advanced stage PBL were immunocompromised with HIV (16), requiring immunosuppression (5), or elderly (13). Despite a 56% CR rate with induction, 69% of patients relapsed. Median PFS was less than 2 years and OS was less than 3 years. The dismal outcomes of pts with PBL suggests that this rare and aggressive subtype of NHL with plasmacytic differentiation requires further evaluation with therapies against plasma cell directed antigens such as CD38, BCMA or SLAMF7. *S Lee & C Dillard contributed equally. Figure 1 Figure 1. Disclosures Steiner: BMS: Research Funding; Seattle Genetics: Research Funding; Rafael Pharmaceuticals: Research Funding. Loghavi: Abbvie: Current equity holder in publicly-traded company; Curio Sciences: Honoraria; Gerson Lehrman Group: Consultancy; Guidepoint: Consultancy; Peerview: Honoraria; Qualworld: Consultancy. Ahmed: Seagen: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Xencor: Research Funding. Patel: Pfizer: Consultancy; Janssen: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Oncopeptides: Consultancy.

Differences in Outcome of Patients with Syncytial Variant Hodgkin Lymphoma (HL) Compared with Typical Nodular Sclerosis HL

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1441-1441
Author(s):  
Tarsheen K. Sethi ◽  
Van T Nguyen ◽  
Shaoying Li ◽  
David S Morgan ◽  
John P. Greer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Complete Response ◽  
Disease Stage ◽  
Cell Transplant ◽  
Advanced Stage ◽  
Bulky Disease ◽  
Free Survival ◽  
Nodular Sclerosis ◽  
Stage Disease

Abstract Introduction: Syncytial variant of nodular sclerosis HL (SV) is a well-described distinct pathologic entity characterized by prominent aggregates of Hodgkin/Reed- Sternberg cells in nodules separated by fibrous collagen bands. Despite its well-known morphologic description, little is known regarding the clinical behavior of the SV. Previous reports suggest that patients with SV often presented with B symptoms and advanced stage disease, however, large series defining the clinical outcome have not been reported so far. We systematically studied the clinical features and outcome of patients with SV and further compared them with patients with typical nodular sclerosis HL (t-NS). Patients and Methods: 167 adult patients (pts.) with Nodular Sclerosis HL were included in our analysis following institutional IRB approval. Differences between the two groups (SV vs. t-NS) were analyzed using Chi- square and t -Student tests. Statistical significance was set at P <0.05. Kaplan Meier method was used to calculate the Progression-free survival (PFS) and overall survival (OS). Log-rank test was used to determine the differences in survival. Statistical analysis was performed using SPSS.22 software. Results: Of the 167 patients, 43 were confirmed as SV based on morphology and immunophenotype. The median age at diagnosis was 31 yrs. (range: 18-75 yrs.) and 85 patients were male (51%). At diagnosis, 100% patients had an ECOG status of 0-1; 39 % had advanced stage disease (stage III and IV); and 48% had B symptoms. 23 % patients presented with bulky disease defined as a mass > 10 cm or a mediastinal mass >1/3 of thorax at T5-T6. 90% patients received ABVD as their initial treatment. The remaining were treated with Stanford V, MOPP or on a clinical trial. 37 % patients received radiation therapy. Furthermore, 63% patients with SV and relapsed disease were treated with high dose therapy followed by stem cell transplant (ASCT). In the SV vs. t-NS comparison, no statistically significant differences were observed between the two groups with regards to age, gender, stage at presentation, B symptoms, bulky disease or favorable features. The rate of complete response (CR) in the SV group was 74% vs. 87% in the t-NS group (P=0.05). Moreover, at a median follow up of 49 months, the median progression free survival (PFS) was inferior in the SV group (17.02 months) compared with the t-NS group (not reached) (P<0.0001; HR = 3.695; 95% CI=3.0-11.07). The median overall survival (OS) was not reached in both groups and was not statistically different [Fig.1&2, P=0.32]. Significant differences in PFS and OS were observed based on stage of disease (early vs. advanced) and achievement of complete response at end of treatment by univariate analysis. In the corresponding multivariate analysis, achievement of CR following completion of treatment was the only independent predictor for OS. Discussion: In summary, our results suggest that SV was associated with a lower rate of complete response to standard ABVD chemotherapy +/- radiation and inferior PFS. Despite the high rate of relapse associated with SV, these patients can be salvaged with standard salvage regimens, ASCT or newer immunomodulatory agents and therefore not compromising OS. Our report suggests that patients with SV should be considered for novel combination immuno-chemotherapies to improve the rate of complete remission and subsequently avoid the need for ASCT. Figure 1. PFS in patients with SV vs. t-NS Figure 1. PFS in patients with SV vs. t-NS Figure 2. OS in patients with SV vs. t-NS Figure 2. OS in patients with SV vs. t-NS Disclosures Reddy: PCYC: Consultancy; ImmunoGen: Consultancy; Gilead: Other: Speaker; Seattle Genetics: Consultancy; Celgene: Consultancy, Research Funding.

scholarly journals Rapid and Deep Hematologic Responses Are Associated with Improved Major Organ Deterioration Progression-Free Survival in Newly Diagnosed AL Amyloidosis: Results from Andromeda

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Ashutosh D. Wechalekar ◽  
Giovanni Palladini ◽  
Giampaolo Merlini ◽  
Raymond L. Comenzo ◽  
Arnaud Jaccard ◽  
...  
Keyword(s):  
Research Funding ◽  
Progression Free Survival ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
Free Survival ◽  
Major Organ ◽  
End Stage

Background: As immunoglobulin light chains present in AL amyloidosis are considered to be toxic to involved organs, especially the heart, rapid and deep hematologic remission with reduction of these light chains with frontline therapy may be crucial to improving long-term clinical outcomes. ANDROMEDA (NCT03201965) is the first phase 3 study in this patient population to evaluate major organ deterioration progression-free survival (MOD-PFS), a composite endpoint of time to end-stage cardiac disease (requiring cardiac transplant, left ventricular assist device, or intra-aortic balloon pump); end-stage renal disease (requiring hemodialysis or renal transplant); hematologic progression per consensus guidelines1; and death. Here, we report the impact of early and deep hematologic responses on MOD-PFS. Methods: ANDROMEDA is a randomized, open-label, active-controlled phase 3 study of patients with newly diagnosed AL amyloidosis who received cyclophosphamide, bortezomib, and dexamethasone (VCd) ± daratumumab subcutaneous (DARA SC; DARA 1800 mg coformulated with recombinant human hyaluronidase PH20 in 15 mL). Key eligibility criteria were newly diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, cardiac stage I-IIIA, eGFR ≥20 mL/min, and absence of symptomatic multiple myeloma. Disease evaluations occurred every 4 weeks during Cycles 1-6. Hematologic responses were adjudicated by an Independent Review Committee. Landmark analyses for response were performed at 1 and 3 months (± 7 days). Analyses of hematologic responses and MOD-PFS were performed on the intent-to-treat analysis set. Patients without a baseline or post-baseline assessment were censored at randomization for the MOD-PFS analysis. Hazard ratios and corresponding 95% confidence intervals were estimated based on Cox proportional hazard model. Results: A total of 388 patients were randomized to DARA-VCd (n=195) or VCd alone (n=193). Baseline characteristics were well balanced between groups. The proportions of patients with heart and kidney involvement were 71% and 59%, respectively. Median follow-up was 11.4 months (range, 0.03-21.3+). For the 1- and 3-month landmark analysis, hematologic response was available for 356 and 289 patients, respectively. Hematologic response rates by treatment group at 1 and 3 months are shown in the Table. MOD-PFS was longer in patients with complete response (CR)/very good partial response (VGPR) at 1 and 3 months vs patients with lower levels of response (Figure). CR/VGPR at 1 and 3 months was associated with reduced risk of death or major organ deterioration in a multivariate analysis adjusting for baseline difference between involved and uninvolved free light chains and cardiac stage, (HR: 0.399, P=0.0006 and HR: 0.262, P=0.0003, respectively). At 1 and 3 months, cardiac and renal response rates were higher in those who achieved early and deep hematologic responses (CR and VGPR). Conclusions: CR/VGPR at 1 and 3 months was associated with a reduced risk of major organ deterioration and death in patients with newly diagnosed AL amyloidosis. These data confirm that initial therapy that achieves rapid and deep hematological responses is essential to improving long-term outcomes in AL amyloidosis. Reference 1. Comenzo RL, et al. Leukemia. 2012;26(11):2317-25 Disclosures Wechalekar: Janssen: Honoraria, Other: Advisory; Caelum: Other: Advisory; Celgene: Honoraria; Takeda: Honoraria, Other: Travel. Palladini:Celgene: Other: Travel support; Jannsen Cilag: Honoraria, Other. Comenzo:Caleum: Consultancy; Unum: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Prothena: Consultancy, Research Funding. Jaccard:Celgene: Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Celgene., Research Funding; Janssen: Consultancy, Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Janssen., Research Funding. Tran:Janssen: Current Employment, Current equity holder in publicly-traded company. Pei:Janssen: Current Employment, Current equity holder in publicly-traded company. Vasey:Janssen Research & Development: Current Employment, Current equity holder in publicly-traded company. Tromp:Janssen: Current Employment, Current equity holder in publicly-traded company. Weiss:Janssen: Current Employment, Current equity holder in publicly-traded company. Vermeulen:Janssen: Current Employment, Current equity holder in publicly-traded company. Kastritis:Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding.

scholarly journals FCR achieves long-term durable remissions in patients with IGHV-mutated CLL

Blood ◽  
2017 ◽  
Vol 130 (21) ◽  
pp. 2278-2282 ◽  
Author(s):  
Chatree Chai-Adisaksopha ◽  
Jennifer R. Brown
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Complete Remission ◽  
Randomized Trials ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Inclusion Criteria ◽  
Free Survival

Abstract In chronic lymphocytic leukemia (CLL) patients with mutated IGHV, 3 recent studies have demonstrated prolonged progression-free survival (PFS) after treatment with fludarabine-cyclophosphamide-rituximab (FCR) chemoimmunotherapy. We performed a systematic review to assess the benefit of FCR for patients with CLL and identified 5 randomized trials that met our inclusion criteria. FCR improved complete remission, PFS and overall survival vs the comparator; median PFS was not reached in the subgroup of CLL patients with mutated IGHV.

ABVD Versus Escalated Beacopp in Advanced Stage Hodgkin's Lymphoma: Results from a Retrospective, Multicenter European Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1565-1565 ◽  
Author(s):  
Patrizia Mondello ◽  
Irene Dogliotti ◽  
Jan-Paul Bohn ◽  
Federica Cavallo ◽  
Simone Ferrero ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Advanced Stage ◽  
Advisory Committees ◽  
Free Survival ◽  
High Risk Patients ◽  
Risk Patients

Purpose: Hodgkin's lymphoma (HL) is a highly curable disease even in advanced-stage, with &gt;90% of long-term survivors. Currently, the standard of care is ABVD (doxorubicin, etoposide, vinblastine and dacarbazine), as it is less toxic and as effective as other more intensive chemotherapy regimens. Alternatively, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) has been proposed as front-line intensified regimen with a better initial disease control and prolonged time to relapse when compared to ABVD. However, this advantage is associated with higher rates of severe hematologic toxicity, treatment-related deaths, secondary neoplasms and infertility. To date, the debate regarding which regimen should be preferred as first line for advanced-stage HL is still ongoing. To shed some light on this open question we compared efficacy and safety of both regimens in clinical practice. Patients and Methods: From October 2009 to October 2018, patients with HL stage III-IV treated with either ABVD or BEACOPP escalated (BEACOPPesc) were retrospectively assessed in 7 European cancer centers. Results: A total of 372 consecutive patients were included in the study. One-hundred and ten patients were treated with BEACOPPesc and 262 with ABVD. The baseline characteristics of the two groups did not differ significantly, except for a higher rate of high-risk patients in the BEACOPPesc group in contrast to the ABVD one (47% vs 18%; p= 0.003). Complete response rate (CR) assessed by PET imaging at the end of the second cycle was 67% and 78% for the ABVD and BEACOPPesc group (p= 0.003), respectively. Thirteen patients of the ABVD group achieved stable disease (SD) and 6 had a progression disease (PD). On the other hand, 4 of the patients in the BEACOPPesc group progressed, another 2 interrupted therapy because life-threatening toxicity. At the end of the therapy, CR was 76% in the ABVD group and 85% in the BEACOPPesc group (p= 0.01). A total of 20% patients in the ABVD group and 14% patients in the BEACOPPesc group received consolidation radiotherapy on the mediastinal mass at the dose of 30Gy. After radiotherapy, the number of patients with CR increased to 79% and 87% in the two groups (p= 0.041), respectively. Thirty-nine patients (35%) in the BEACOPPesc group required dose reduction of chemotherapy due to toxicity compared to 12 patients (5%; p= &lt;0.001) in the ABVD group. Overall, the rate of severe toxicities was higher in the BEACOPPesc group in comparison with the ABVD cohort. In particular, there was a significant increased frequency of acute grade 3-4 hematologic adverse events (neutropenia 61% vs 24%; anemia 29% vs 4%; thrombocytopenia 29% vs 3%), febrile neutropenia (29% vs 3%), severe infections (18% vs 3%). Myeloid growth factors were administered to 85% and 59% of patients in the BEACOPPesc group compared to the ABVD group. Blood transfusions were required in 51% and 6% of patients in the BEACOPPesc group compared to the ABVD cohort. Progression during or shortly after treatment occurred in 5 patients in the BEACOPPesc group (4%) and in 16 patients in the ABVD group (6%; p= 0.62). Among the 96 patients who achieved a CR after BEACOPPesc and radiotherapy, 8 relapsed (8%), compared to 29 of 208 patients in the ABVD group (14%; p= 0.04). At a median follow-up period of 5 years, no statistical difference in progression free survival (PFS; p=0.11) and event-free survival (EFS; p=0.22) was observed between the BEACOPPesc and ABVD cohorts. Similarly, overall survival (OS) did not differ between the two groups (p=0.14). The baseline international prognostic score (IPS &lt;3 vs ≥ 3) significantly influenced the EFS with an advantage for the high-risk group treated with BEACOPPesc (Figure 1A; p=0.03), but not the PFS (Figure 1B; p=0.06) and OS (Figure 1C; p=0.14). During the follow-up period, in the BEACOPPesc group one patient developed myelodysplasia and one acute leukemia. Second solid tumors developed in one patient in the ABVD group (lung cancer) and one in BEACOPPesc group (breast cancer). Conclusion: We confirm that the ABVD regimen is an effective and less toxic therapeutic option for advanced-stage HL. Although BEACOPP results in better initial tumor control especially in high-risk patients, the long-term outcome remains similar between the two regimens. Disclosures Ferrero: EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; Servier: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Speakers Bureau. Martinelli:BMS: Consultancy; Pfizer: Consultancy; ARIAD: Consultancy; Roche: Consultancy; Novartis: Consultancy. Willenbacher:European Commission: Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Myelom- und Lymphomselbsthilfe Österreich: Consultancy, Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Science: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; IQVIA: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; oncotyrol: Employment, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fujimoto: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tirol Program: Research Funding; Abbvie: Consultancy, Honoraria; Sandoz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

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