scholarly journals Observational Study Alternating R-CHOP21 and R-Cytarabine (3+3 Cycles) for Patients with Newly Diagnosed Mantle Cell Lymphoma Not Eligible for High-Dose Therapy: A Czech Lymphoma Study Group Trial Preliminary Results

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1720-1720
Author(s):  
Pavel Klener ◽  
Eva Fronkova ◽  
Robert Pytlik ◽  
Marketa Kalinova ◽  
Kristina Forsterova ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
High Dose Therapy ◽  
Pet Ct ◽  
Mantle Cell ◽  
Grade 3

Abstract Background: Mantle cell lymphoma (MCL) is an aggressive type of B-cell non-Hodgkin lymphoma characterized by frequent relapses and adverse prognosis. Implementation of high-dose cytarabine (HDAC) and incorporation of anti-CD20 antibody rituximab (R) into induction and maintenance, and consolidation with high-dose therapy and autologous stem cell transplantation (HDT-ASCT) significantly improved pt´s outcome. Therapy of the elderly or comorbid (not eligible for HDT-ASCT) is largely based on R-CHOP or R-bendamustin induction with or without R maintenance. Minimal residual disease (MRD) assessment by quantitative PCR (qPCR) from peripheral blood or bone marrow (BM) has emerged as a powerful molecular marker of outcome. Based on the results of the younger pts some centers adopted the use of HDAC in elderly as well, but no data has been presented yet. Aim: We initiated the observational study as a non-intervention, multi-center trial with the primary objectives to prospectively evaluate efficacy of alternating R-CHOP21 and R-HDAC (1 or 2 g / m2, 2 doses a 24 hours) in newly diagnosed MCL pts not eligible for HDT-ASCT. Methods: Primary endpoints were overall response rate (ORR) by PET-CT, and MRD assessment by qPCR after completion of induction. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. The choice between 1 and 2 g / m2 cytarabine was left at investigator´s discretion, as well as the rituximab maintenance. Patients with known cardiac co-morbidity could be treated with R-COEP (etoposid 50 mg / m2, D1-D3) instead of R-CHOP. Exclusion criteria included eligibility to HDT-ASCT, ECOG≥ 4, and CNS involvement. Results: Altogether 61 pts (38 men and 23 women, ratio 1.7:1) were enrolled into the study between 16-JUN-2011 and 18-MAR-2014. Median age was 70 years both for men and women. 91.5%, and 80% pts presented with stage 3/4 disease, and infiltration of BM, resp. According to the MIPI, 55.7%, 39.4%, and 4.9% pts had high, intermediate and low risk disease, resp. B-symptoms were recorded in 33.3% of pts. 76.8% and 24.2% pts were diagnosed from the lymph node, and trephine biopsy, resp. 62.8%, 27.9%, and 9.3% pts presented with classical, pleomorphic and blastoid variant MCL, resp. Ki67/MIB1 ≥ 30% was observed in 38% of pts. Bulky disease >5cm, and >10cm, was noticed in 31% and 13% pts. Spleen involvement was observed in 53% pts. Extra-nodal involvement other than BM was histologically confirmed in 11.5% pts. R-CHOP was used in 88% pts (12% pts received R-COEP), 86% pts received 2g / m2 cytarabine (14% pts 1g / m2). 86.3% pts with response were treated with R maintenace. Only one patient was excluded from the study due to unacceptable toxicity. 57.7% pts developed grade 3/4 hematologic toxicity (neutropenia, anemia or thrombocytopenia). Grade 3/4 non-hematologic toxicity occurred in 27.3% pts. All pts had PET-CT restaging after completion of induction. Overall response rate (CR+PR) reached 91.7%. CR and PR rate by PET was 76.7%, and 15%, resp. SD, and progression on therapy was noticed in 3.3%, and 5.0%, resp. Samples for MRD assessment were collected from 41 out of 54 pts, who completed induction and achieved response (CR or PR). At the time of abstract submission 21, 7, and 7 (out of 36 so far evaluated pts) were MRD negative, MRD positive-not quantifiable, and MRD positive-quantifiable, resp. With the median follow-up 19.1 month, there were 7 progressions and 6 deaths. 2-year PFS and OS probability were 83.9% and 88.1%. Conclusion: Alternation of R-CHOP and R-HDAC in newly diagnosed elderly or co-morbid MCL pts represents a promising, very effective and well-tolerated treatment approach that induces high ORR, and MRD negativity. Grant Support: IGA-MZ NT/13072-4, PRVOUK-27/LF1/1 Disclosures No relevant conflicts of interest to declare.

Phase II study of pegylated liposomal doxorubicin (PLD), low-dose dexamethasone (DEX), and lenalidomide (LEN) in patients with newly diagnosed (ND) multiple myeloma (MM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8518-8518
Author(s):  
R. Baz ◽  
M. A. Hussein ◽  
D. Sullivan ◽  
J. Raychaudhuri ◽  
L. Ochoa ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
High Dose ◽  
Hematologic Toxicity ◽  
High Dose Therapy ◽  
Overall Response ◽  
Dose Therapy ◽  
Grade 3

8518 Background: We previously reported the results of a phase I/II trial of PLD, low dose DEX and LEN in patients with relapsed and refractory MM in which the MTD of LEN was 10 mg (for 21 of 28 days) and the overall response rate was 75% with 29% of patients achieving nCR or better (Ann Oncol 2006). Accordingly we evaluated this regimen in ND MM. Methods: We hypothesized that patients with ND MM would tolerate this combination better. Accordingly, patients received PLD (40 mg/m2 on day 1), DEX (40 mg on days 1–4) and LEN (25 mg Days 1–21) every 28 days (for 2 cycles beyond best response: 4–8 cycles). Prophylactic low dose aspirin, acyclovir and fluoroquinolone were recommended. Patients not eligible or not wishing to proceed with high dose therapy continued on the tolerated dose of LEN and DEX until disease progression or unacceptable toxicity. Results: Between 2/2008 and 8/2008, 31 of a planned 60 patients were enrolled. 2 patients were screen failures and are not included in subsequent analysis. The mean age was 64 years (41–82) and 58% were males. The median β2microglobulin was 2.8 mg/dL (34% had β2m>3.5). Using the modified SWOG criteria and after a median of 4 cycles of therapy, the overall response rate was 80% with 40% VGPR and better. Two patients had stable disease and 3 patients had progressive disease. Grade 3/4 hematologic toxicity was as follows: neutropenia (48%), anemia (10%), thrombocytopenia (7%). Grade 3/4 non-hematologic toxicity included: Fatigue (21%), infections and febrile neutropenia (20%, only 1 patient with febrile neutropenia), venous thromboembolic events (10%). 14 patients went off study including 8 patients to proceed with high dose therapy. Conclusions: The combination of PLD, LEN and DEX is an active regimen in patients with ND MM. Due to the unexpected higher rates of neutropenia and fatigue, the dose of PLD will be decreased to 30 mg/m2 every 28 days. Updated results will be presented at the time of the meeting. [Table: see text]

A Phase 2 Study of Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) Plus Rituximab in Newly Diagnosed, Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3698-3698
Author(s):  
Robert W. Chen ◽  
Leslie Popplewell ◽  
Paul Frankel ◽  
Tanya Siddiqi ◽  
Joel Conrad ◽  
...  
Keyword(s):  
Median Time ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Newly Diagnosed ◽  
Overall Response ◽  
Mantle Cell ◽  
Time To Treatment Failure ◽  
Indolent Lymphomas

Abstract Abstract 3698 Background: Follicular, marginal zone and mantle cell lymphomas are indolent lymphomas that tend to recur with decreasing intervals of remissions. Vorinostat (SAHA) is an orally administered hydroxamic acid histone deacetylase inhibitor with activity against class I and II deacetylases. Single agent vorinostat has an overall response rate of 29% in all indolent lymphomas (47% in follicular lymphoma) with prolonged disease free survival. (Kirschbaum, JCO 2009) Preclinical data suggests enhanced activity for the combination of vorinostat plus rituximab. We report the clinical results of a phase II study of the combination of vorinostat plus rituximab. Methods: These are the updated results of our two-stage phase II study in patients with newly diagnosed, relapsed or refractory follicular, marginal zone, or mantle cell lymphoma. Vorinostat is given at 200 mg PO twice daily for 14 consecutive days on a 21 day cycle. Rituximab is given on day 1 of each cycle. CT scanning and/or FDG-PET are performed after every three cycles. Patients may have received up to four prior chemotherapy regimens including tositumomab or ibritumomab; previous autologous transplant is allowed. The primary endpoint was the overall response rate according to Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Results: 26 eligible patients were accrued thus far. See Table 1 for baseline characteristics. Outcomes are available on 23 patients: the overall response (CR+PR) rate thus far is 35% (8/23) The CR rate for all patients is 30% (7/23). The response rate for untreated patients (5 FL, 1 MZL) is 66.6% (4/6, all CR). The other two patients remain on study with prolonged stable disease. The formal response rate thus far for relapsed/refractory patients is 23.5% (4/17). By histology, the response rate is 35% (7/19) for FL, 0/2 for mantle cell, 1/1 for MZL, and 0/1 for lymphoplasmacytic lymphoma. The median time to achieve CR is 12 months. Of the 7 patients who achieved CR, 3 have relapsed while off treatment and were retreated with vorinostat plus rituximab. 1 achieved CR and is 13 months into treatment, 1 achieved PR and is 23 months into treatment, while 1 transformed both to Hodgkin lymphoma and diffuse large B cell lymphoma (biopsy proven). The median time to treatment failure for patients achieving CR is 38 months, with 6 ongoing, including the two retreated patients (14, 27, 29, 29, 31, and 35 months). Of non-responders, 8 patients achieved stable disease for at least 9 cycles with one SD for 63+ cycles. The disease control rate for > 9 cycles (CR+PR+SD) is 69.6% (16/23). Five patients were taken off study for reasons other than progression (2 patients choice, 1 to transplant, 1 for concomitant medication violation, and 1 physician choice). The median time to treatment failure for all patients was 9 months (95% CI, 6 months, NR). Treatment was well tolerated. Grade 4 toxicities possibly attributable to study drug include neutropenia (n=1), asymptomatic thrombosis (n=4), and thrombocytopenia (n=2). Grade 3 possibly related toxicities include fatigue (n=7), hyperglycemia (n=3), dehydration (n=2), and one each of thrombocytopenia, neutropenia, anemia, hypophosphatemia, hypotension, pneumonia, diarrhea, diverticulitis, and syncope. The thromboses were nonclinical pulmonary embolism discovered incidentally on CT scan, and resulted in amending the study to include 40 mg enoxaparin as prophylaxis, resulting in no further thromboses identified. Conclusions: The combination of vorinostat with rituximab is well tolerated, and shows encouraging activity against newly diagnosed, as well as relapsed/refractory indolent lymphoma. Durable responses can be achieved. Extended treatment with this combination is feasible and well tolerated, and retreatment with this regimen is efficacious in previous responders who relapsed. Disclosures: Off Label Use: Use of vorinostat in combination with rituxan for indolent B cell lymphomas.

First Interim Efficacy and Safety Analysis of an International Phase III Randomized Trial in Newly Diagnosed Systemic Peripheral T-Cell Lymphoma Treated with Chemotherapy with or without Alemtuzumab and Consolidated by High Dose Therapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 57-57 ◽  
Author(s):  
Francesco d'Amore ◽  
Sirpa Leppä ◽  
Maria Gomes da Silva ◽  
Thomas Relander ◽  
Peter De Nully Brown ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Phase Iii ◽  
High Dose ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
High Dose Therapy ◽  
Peripheral T Cell Lymphoma ◽  
Free Survival ◽  
Younger Patients ◽  
Grade 3

Abstract Abstract 57 Background The ACT trial (ACT-1, younger patients aged 18–60 yrs and ACT-2, elderly patients aged >60 yrs) is the first international randomized phase III trial in newly diagnosed primary systemic peripheral T-cell lymphoma (PTCL). It tests, in both younger and elderly patients, the efficacy of the addition of alemtuzumab (ALZ) to 6 courses of bi-weekly CHOP followed, only in younger patients (ACT-1), by high-dose therapy with autologous stem cell rescue. A dose reduction amendment tapering the cumulative ALZ dose from 360 mg (30 mg on days 1 and 2 of CHOP courses 1–6) to 120 mg (30 mg on day 1 of CHOP courses 1–4), respectively, was introduced early on due to two cases of systemic fungal infection (Blood 2011,118;4110). To date, the trial has accrued a total of 186 patients (ACT-1 n=98; ACT-2 n=88). Aim Here, we present the results from the first interim efficacy and safety analysis of the ACT-1 trial based on the first 68 randomized patients. Results Of the 68 patients, 63 had a complete set of treatment data. The median follow-up was 15 months (range 0.5–42 months). Thirty-two patients belonged to the experimental arm (exp) and 31 to the standard arm (std). Of the 32 patients treated according to exp, 4 received the higher dose of ALZ and 28 the lower. Treatment arms were well balanced with regard to main prognostic features such as age (std: median 53 yrs, range 21–60 yrs; exp: median 50 yrs, range 22–64 yrs; p=0.705), IPI subgroups (std: low 10%, low-intermediate 51%, intermediate-high 29%, high 10%; exp: low 12%, low-intermediate 44%, intermediate-high 19%, high 25%; p=0.392), advanced clinical stage (std: stage III-IV 94%; exp: 97%; p=0.613), performance status ECOG>1 (std: 23%; exp: 28%; p=0.613), elevated LDH (std: 68%; exp: 69%; p=0.932), presence of B-symptoms (std: 68%; exp: 75%; p=0.524), bulky disease (std: 13%; exp: 13%; p=1.0) and bone marrow involvement (std: 39%; exp: 31%; p=0.535). Histological subtypes were also similarly distributed among both treatment arms (std: PTCL-NOS 55%, AILT 23%, other 22%; exp: PTCL-NOS 56%, AILT 28%, other 16%). No cases of anaplastic large cell PTCL (regardless of ALK-protein status) were included. Neither of the treatment cohorts showed significant treatment delay. The median duration of chemotherapy (calculated for 5 bi-weekly cycles of an expected cumulative duration of 70 days) for non-ALZ vs. ALZ-treated patients was 73 vs. 81 days, respectively. No suspected unexpected serious adverse reactions (SUSARs) were reported. Grade 4 leucopenia was more frequent in ALZ-treated patients (std: 24%, exp: 69%; p=0,001), whereas grade 3–4 anemia and grade 3–4 thrombocytopenia were not significantly different between treatment arms (anemia, std: 19%, exp: 31%; p=0,278; thrombocytopenia, std: 20%, exp: 12%, p=0,682). Non-hematological toxicity unrelated to infectious complications was mild and had a similar frequency in both arms. The number of serious adverse events (SAEs) per patient was 0.86 for patients treated at post-amendment ALZ dose levels, representing a significant reduction compared to the pre-amendment value (3.25), and 0.46 for patients treated in the control arm (p=0.002). The frequency of bacterial and fungal infections (grade ≥3) was similar in both treatment arms. ALZ treated patients had more viral events (9/32; 28% vs. 3/31; 10%), mainly (6 out of 9) consisting of asymptomatic cytomegalovirus reactivations. The overall (non-arm specific) 1-year event-free survival (primary end-point), progression-free survival and overall survival were 55% (95% CI: 42%-67%), 54% (95% CI: 42%-67%) and 78% (95% CI: 67%-88%), respectively. Conclusion The safety profile of the current standard and experimental treatment schedules, as well as the interim outcome results, support a continuation of the trial. A final analysis will be performed in Q2 2015. Disclosures: Jantunen: Genzyme: Has participated in EU Leadership meeting organized by Genzyme as well as Medical Advisory Board meeting organized by Genzyme Other, Honoraria.

Bortezomib, Rituximab, and Dexamethason (BORID) as Salvage Treatment in Relapsed/Refractory Mantle Cell Lymphoma: Sustained Disease Control in Patients Achieving a Complete Remission.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2578-2578 ◽  
Author(s):  
Johannes Drach ◽  
Hannes Kaufmann ◽  
Oskar Pichelmayer ◽  
Verena Sagaster ◽  
Sonja Holzer ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Control ◽  
Mantle Cell Lymphoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
High Dose ◽  
Synergistic Activity ◽  
Overall Response ◽  
Mantle Cell

Abstract Background: Bortezomib (B) belongs to a new class of anti-cancer agents, the proteasome inhibitors, and has documented activity in multiple myeloma and mantle cell lymphoma (MCL). Preclinical studies suggest that B has synergistic activity with rituximab (R), which provides a rationale for the exploration of treatment combinations. We therefore evaluated the activity and safety of B in combination with R and dexamethasone (BORID) in patients with relapsed and refractory MCL (phase II trial). Methods: A treatment cycle consists of B at 1.3 mg/m2 administered on days 1, 4, 8, and 11, R at 375 mg/m2 administered on day 1, and dexamethasone 40 mg orally on days 1 to 4. Cycles are repeated every 3 weeks for a total of 6 treatment cycles. Patients (pts) achieving a response received 4 additional doses of R as maintenance (every 8 weeks). Pts with progressive MCL after at least one prior line of therapy (including CHOP or a CHOP-like regimen) were eligible. Results: We have completed enrollment of 16 pts (median age, 67 years; range, 48 to 75 years) after a median of 3 lines of prior therapies (range, 1 to 6, prior rituximab in 88%; thalidomide in 50%; high-dose therapy in 31%; a fludarabine-containing regimen in 31%). Median time between start of frontline therapy and study inclusion was 42 months (range, 11 to 98 months). Severe adverse events (> grade II) included infections (herpes zoster in 2 pts, bacterial pneumonia, mucosal candidiasis), peripheral neuropathy (3 pts), fatigue (2 pts) and vasculitic skin infiltrates in 3 pts. Thrombopenia (< 50 G/L) occured in 2 pts. All adverse events were managable by standard means of supportive care and prolongation of the treatment interval between cycles. Overall response rate was 69% (11 of 16 pts), with 6 pts achieving a CR (38%; confirmed by PET-scan in 5 pts) and 5 pts reaching a PR. Skin infiltrates (histologically proven T-cell infiltrates) preceded achievement of CR in 2 pts. Remission status appeared to be associated with progression-free survival (PFS): Patients in CR had longer PFS (29+, 24+, 21+, 12+, 12, and 10+ months) compared to patients in PR (median 8.5 months, range 6 – 15). Conclusions: BORID has promising activitiy (69% overall response rate; CR rate 38%) and managable toxicity in this patient population with predominantly heavily pretreated MCL. Achievement of a CR emerged as an important factor for sustained disease control. Further evaluation of this regimen, in particular in pts at an earlier phase of the disease, is warranted.

Clinical Efficacy of the Rivbd Combination for Refractory/Relapsed (R/R) Mantle Cell Lymphoma (MCL) Patients: A Retrospective Study of the French Lysa Group

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1111-1111
Author(s):  
Caroline Régny ◽  
Sandra Malak ◽  
Guillaume Manson ◽  
Clementine Sarkozy ◽  
Aline Clavert ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Salvage Therapy ◽  
Older Patients ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Overall Response ◽  
Mantle Cell ◽  
Grade 3

Abstract Background There is no standard treatment for R/R MCL that fail first line treatment. Non cross resistant regimens are usually used, which provided sometimes good overall response rate (until 93%) but with a minor disease control (PFS<2years). [1] The main objective of these salvage regimens is to bypass disease resistance, to obtain more profound ( deep or durable) response and to ensure, in younger patients, the option of performing autologous or allogenic stem cell transplantation. For older patients prolonging disease free survival is the aim. The new combination RiVBD (Rituximab-Bendamustine-Bortezomib-Dexametasone) has recently shown to be an effective regimen in frontline for eldery patients with a good tolerability profile (NCT 01457144). [2] Many French centers have also used this association for the R/R patients. Aim To explore the efficacy of the RiBVD regimen in the salvage therapy setting following failure of one, two or more prior treatments. Methods We proposed to all French LYSA partner centers a survey to retrospectively evaluate the efficacy of the RiBVD regimen in R/R MCL patients, regardless of prior treatments used. The RiBVD regimen comprises : Rituximab 375mg/sqm D1, Bendamustine 90mg/sqm D1 and D2, bortezomib 1,3mg/sqm D1, D4, D8, D11 and dexamethasone 40 mg D2. Analysis was performed in June 2016. Results From January 2012 to December 2015, 49 patients from 17 French hematological centers were recruited to the study. The median age was 72 years (50-91y) with 14 young (<65y) and 35 older patients (> 65y). Thirty eight cases presented with classic MCL variant and 11 had a blastoid variant. All patients but one were CD20+, CD5+, CD10- and were positive CYCLIN D1 expression and/or the t(11;14)(q13;q32). Eighteen patients presented a t(11;14) (q13;q32).The CYCLIN D1 negative patient had a t(11;14). Treatment history: Twenty seven patients received RiBVD in second line, 12 in third line and 10 patients after the third lines. Twenty two patients were refractory to their previous line and 27 were in relapse. Before RiBVD 44/49 patients (90%) had received high dose cytarabine, 3 Ibrutinib and 14 patients were intensified (11 at diagnosis, 3 in relapse). Efficacy: The global overall response rate (ORR) was 75% (37/49, 23 CR and 14 PR). For patients treated in 2nd line, the ORR was 85% (23/27, 16 CR and 7 PR), in 3nd line 58% (7/12, 4 CR and 3 PR), and 70% (7/10) for the others (3 CR and 4 PR). Young patients had an ORR of 64% (9/14, 8 CR, 2 RP) and elderly pts 77% (27/35, 15 CR, 12 PR). For relapsed and refractory pts the ORR was respectively 85% (23/27, 15 CR and 8 PR) and 63% (14/22 with 8 CR and 6 PR). For Classic and blastoid variants the ORR was 81.5% (31/38, 20 CR and 11 PR) and 54% (6/11, 3 CR and 3 PR) respectively. Note that 2/3 pts receiving RiBVD regimen post Ibrutinib failure, reached PR (n=2) and showed stable disease (n=1). Major toxicities were seen in 31 pts (63%) with grade 3/4 hematological toxicity in 22 pts, grade 3 neurotoxicity in 3 pts, grade 3/4 cardiotoxicity in 3 pts, grade 3/4 infectious complications in 8 pts, grade 4 fatigue in 3 pts and grade 3 digestive-tract or cutaneous toxicity in one pt each. At the update point, 17 pts had died, 15 for lymphoma progression, 2 for TRM while experiencing a CR (infectious and leukemia). The follow-up of the 32 surviving pts was 14.5 month. The median PFS was 9 months for the 49 pts. The PFS was statistically affected by the pathologic type (classic vs Blastoid, p=0.03), the number of prior treatment (one vs >one, p=0.04) and response to RiBVD (CR vs PR vs no response, p<0.0001 with a median PFS not reached for CR pts, 6 months for PR and 2 months for no response. The age (<65 vs >65) or the state (relapse or refractory) at the time of RiBVD had no impact on PFS. Conclusion The RiBVD regimen which shows remarkable efficacy in frontline treatment of elderly MCL pts, shows potential as a salvage therapy for refractory or relapsed MCL following cytarabine based treatment. This is particularly true for the 47% of patients achieving CR for which 2 years PFS was 71% regardless of their age. 1. Cheah CY, Seymour JF, Wang ML. Mantle Cell Lymphoma. J Clin Oncol 2016; 34: 1256-1269. 2. Gressin R, Callanan M, Daguindau N et al. Frontline therapy with the RiBVD regimen elicits high Clinical and Molecular Response Rates and long PFS in elderly patients Mantle Cell Lymphoma (MCL); Final Results of a Prospective Phase II trial by the LYSA group. Blood 2014. Disclosures No relevant conflicts of interest to declare.

SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group

Blood ◽  
2012 ◽  
Vol 120 (15) ◽  
pp. 2973-2980 ◽  
Author(s):  
Yok-Lam Kwong ◽  
Won Seog Kim ◽  
Soon Thye Lim ◽  
Seok Jin Kim ◽  
Tiffany Tang ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Remission Rate ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Newly Diagnosed ◽  
Natural Killer T Cell ◽  
Grade 3 ◽  
Killer T Cell

Abstract Natural killer/T-cell lymphoma is rare and aggressive, with poor outcome. Optimal treatment remains unclear. A novel regimen dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE) showed promise in phase 1/2 studies with restrictive recruitment criteria. To define the general applicability of SMILE, 43 newly diagnosed and 44 relapsed/refractory patients (nasal, N = 60, nonnasal, N = 21; disseminated, N = 6; male, N = 59; female, N = 28) at a median age of 51 years (23-83 years) were treated. Poor-risk factors included stage III/IV disease (56%), international prognostic index of 3 to 5 (43%), and Korean prognostic scores of 3 to 4 (41%). A median of 3 (0-6; total = 315) courses of SMILE were administered. Significant toxicities included grade 3/4 neutropenia (N = 57; 5 sepsis-related deaths); grade 3/4 thrombocytopenia (N = 36); and nephrotoxicity (N = 15; 1 acute renal failure and death). Interim analysis after 2 to 3 cycles showed complete remission rate of 56%, partial remission rate of 22%, giving an overall response rate of 78%. On treatment completion, the overall-response rate became 81% (complete remission = 66%, partial remission = 15%). Response rates were similar for newly diagnosed or relapsed/refractory patients. At a median follow-up of 31 months (1-84 months), the 5-year overall survival was 50% and 4-year disease-free-survival was 64%. Multivariate analysis showed that international prognostic index was the most significant factor impacting on outcome and survivals.

scholarly journals Percutaneous Hepatic Perfusion (PHP) with Melphalan in Liver-Dominant Metastatic Uveal Melanoma: The German Experience

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 118
Author(s):  
Cornelia L. A. Dewald ◽  
Mia-Maria Warnke ◽  
Roland Brüning ◽  
Martin A. Schneider ◽  
Peter Wohlmuth ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Response To Therapy ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Hepatic Perfusion ◽  
Grade 3 ◽  
High Dose Melphalan ◽  
Percutaneous Hepatic Perfusion

Percutaneous hepatic perfusion (PHP) delivers high-dose melphalan to the liver while minimizing systemic toxicity via filtration of the venous hepatic blood. This two-center study aimed to examine the safety, response to therapy, and survival of patients with hepatic-dominant metastatic uveal melanoma (UM) treated with PHP. A total of 66 patients with liver-dominant metastasized uveal melanoma, treated with 145 PHP between April 2014 and May 2020, were retrospectively analyzed with regard to adverse events (AEs; CTCAE v5.0), response (overall response rate (ORR)), and disease control rate (DCR) according to RECIST1.1, as well as progression-free and overall survival (PFS and OS). With an ORR of 59% and a DCR of 93.4%, the response was encouraging. After initial PHP, median hepatic PFS was 12.4 (confidence interval (CI) 4–18.4) months and median OS was 18.4 (CI 7–24.6) months. Hematologic toxicity was the most frequent AE (grade 3 or 4 thrombocytopenia after 24.8% of the procedures); less frequent was grade 3 or 4 hepatic toxicity (increased aspartate transaminase (AST) and alanine transaminase (ALT) after 7.6% and 6.9% of the interventions, respectively). Cardiovascular events included four cases of ischemic stroke (2.8%) and one patient with central pulmonary embolism (0.7%). In conclusion, PHP is a safe and effective salvage treatment for liver-dominant metastatic uveal melanoma. Serious AEs—though rare—demand careful patient selection.

Rituximab-EPOCH, an Efective Front-Line Therapy for Mantle Cell Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4490-4490
Author(s):  
Andres Palacios ◽  
Andres Lopez ◽  
Antonio Salar ◽  
Marta Cervera ◽  
Merche Gironella
Keyword(s):  
Prospective Study ◽  
Mantle Cell Lymphoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Line Therapy ◽  
Mantle Cell ◽  
Grade Iii

Abstract Introduction: Mantle-cell lymphoma accounts for 3–10% of non-Hodgkin’s lymphomas, with a median survival not exceeding of 3–4 years and its remains incurable with conventional therapy. CHOP plus Rituximab can induce a molecular complete response in 36% of patients. More aggressive combinations, as Hyper CVAD achieved an overall response rate of 97% with 87 of complete response, data no further confirmed in other studies in which Hyper-CVAD together with Rituximab achieve an overall response rate of 62.5%, with 33% of complete responses (CR). Being toxicity high mainly in elderly patients. Infusional chemotherapy combinations have shown efficacy in mantle-cell lymphoma (as VAD). Based this premise and in the efficacy of infusional R-EPOCH in aggressive lymphomas (DLBCL and PMBCL) we have conducted a compassionate prospective study of non-adjusted infusional EPOCH-R in patients with mantle -cell lymphoma as first-line therapy. Aim: To evaluate the clinical activity and toxicity of non-escalated infusional EPOCH-R as upfront therapy in patients newly diagnosed of mantle-cell lymphoma. Patients and methods: Herein, 12 patients of an ongoing compassionate prospective study in newly diagnosed patients with mantle-cell lymphoma are reported. EPOCH-R consisted on Rituximab 375 mg/m2 day 1, vincristine 0.4 mg plus doxorubicine 40 mg/m2 plus etoposide 50 mg/m2 days 1 to 4 in four day continuous infusion, cyclophsphamide 750 mg/m2 day 5, and prednisone 60 mg/m2 for 5 days, repeated every 21 days if feasible for 6 cycles. The median age of 65 yrs (range, 49–76). 50% of patients were males. 91% of patients presented with an Ann Arbor stage III–IV, high LDH in 50% of cases, leukemic status in 66.6%, Bone Marrow involvement in 66.6% and ECOG <2 was present in 91% of the cases. Results: The response rate to EPOCH-R was 100% with 91% complete response (11 out of 12 patients). Neutropenia grade III–IV was observed in 16% of cases and anemia grade III–IV in 16% of cases. One case of neutropenic fever and two cases of grade III diarrhoea. Conclusions: These preliminary results suggest that EPOCH-R is an effective as other more aggressive combinations and probably with less toxicity profile. More experience and longer follow-up is warranted to confirm this initial appealing experience.

Cladribine Plus Rituximab Is An Effective Therapy for Newly Diagnosed Mantle Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4910-4910
Author(s):  
Stephen Spurgeon ◽  
Talia Pindyck ◽  
Marc M Loriaux ◽  
Craig Okada ◽  
Kamal Abbi ◽  
...  
Keyword(s):  
Complete Remission ◽  
B Cell ◽  
Initial Treatment ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Treatment Strategies ◽  
Newly Diagnosed ◽  
Mantle Cell

Abstract Abstract 4910 Background: Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma that is incurable with standard chemotherapy and remains a therapeutic challenge. Despite improved outcomes in MCL there is no consensus on the best initial treatment. Options vary from aggressive treatment strategies that incorporate multi-agent induction chemotherapy and consolidative transplant to less intensive treatment strategies that utilize alkylators, purine nucleoside analogues, and the monoclonal antibody rituximab. Although, higher response rates have been seen with aggressive approaches, their impact on overall survival is not yet fully appreciated and many patients are not candidates for such approaches. Thus, finding less intensive induction regimens is imperative. The combination of rituximab plus cladribine has shown activity across a number of B-cell malignancies and the NCCN treatment guidelines currently include this regimen for the initial treatment of MCL; noting that there are few data available to substantiate this recommendation. The largest prospective experience (n=29) with R-cladribine for the initial treatment of MCL comes from the North Central Cancer Group. They reported an overall response rate (ORR) of 66% with a 52% complete remission (CR) rate and a 2 year progression free survival (PFS) of 43%. Given its therapeutic potential and increasing popularity, more data are needed to verify the benefits of the R-cladribine regimen. Therefore, to explore the role of R-cladribine in the treatment of newly diagnosed MCL, we performed a retrospective chart review of patients with newly diagnosed MCL treated with R-cladribine. Methods: We reviewed the charts of 31 patients with newly diagnosed MCL initially seen at two university hospitals and at an associated VA that were treated with R-cladribine. One patient had been previously treated with 2 cycles of R-CHOP;, all other patients were untreated. All patients had measurable disease and follow up imaging (CT and/or PET/CT scans) before and at the completion of therapy. Post treatment bone marrow biopsies were not available for all patients. Chemotherapy included: cladribine 5mg/m2 given over two hours on days 1–5; and rituximab given on days 1, 8, 15, and 22 with the first cycle and then on day 1 with subsequent cycles. Each cycle was 28 days for up to a total of 6 cycles. Patients with an initial response received maintenance rituximab. Results: The median age of our cohort was 67 years (48-86) with 42% of patients ≥ 65 years. All patients had advanced stage disease (stage ≥ 3) and the majority of patients had poor risk disease. For example, 20/31 (65%) of patients had high FLIPI (≥ 3) and11/31 (37%) had high MIPI (≥ 6). Of the 24 patients in whom beta2-microglobulin was available, 11 (46%) had levels ≥ 3.5 mg/L. The overall response rate (ORR) was 87% with 19/31(61%) of patients achieving a complete remission (CR/CRu). At a median follow up of 21.5 months (2-85 months) the 2 year PFS rate is 65% and the OS rate is 74%. For those subjects achieving a CR/CRu with a median follow up of 23 months, 1/19 (5.3%) has relapsed. No significant trends were seen regarding response rate and pre-treatment disease defining parameters including Ki67, beta2-microglobulin, FLIPI, or MIPI. However, CR was associated with improved survival (p = <.0001) while high MIPI was associated with worse survival (p=0.0317). There was one toxic death (neutropenic sepsis) related to treatment. Conclusion: The combination of rituximab plus cladribine appears to be an effective initial therapy in MCL. The higher response rates seen in this series may be the result of patient selection and/or increased rituximab exposure. Rituximab maintenance may also be an important component of ongoing disease control in responding patients. These data support the ongoing evaluation of rituximab plus cladribine in combination with novel agents. Prospective single arm studies incorporating R-cladribine with other novel agents such as vorinostat, bortezomib, or temsirolimus are ongoing. Disclosures: No relevant conflicts of interest to declare.

A phase II trial of gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOX) for patients with refractory or relapsed non-Hodgkin's lymphoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8559-8559
Author(s):  
B. Park ◽  
W. Kim ◽  
H. Eom ◽  
J. Kim ◽  
S. Oh ◽  
...  
Keyword(s):  
B Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Salvage Regimen ◽  
Non Hodgkin Lymphoma ◽  
Lymphoma Treatment ◽  
Mantle Cell ◽  
Grade 3

8559 Background: Gemcitabine combined with cisplatin has been known as an effective regimen for lymphoma treatment in salvage setting. However, this regimen has the modest response with severe nephrotoxcity and neurotoxicity, especially to heavily treated patients. We investigated the response rate and toxicity of gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOx) for recurrent or refractory aggressive B-cell non-Hodgkin lymphoma (NHL), looking for the more effective and less toxic therapy. Methods: Patients with recurrent or refractory diffuse large B-cell NHL or mantle cell lymphoma, measurable disease, and more than one previous chemotherapy regimen were eligible. Treatment consisted of gemcitabine 1000 mg/m2 intravenously (i.v.) on Days 1 and 8, ifosfamide 2000 mg/m2 i.v. on Day 1, dexamethasone 40 mg orally on Days 1–4, and oxaliplatin 130mg/m2 i.v. on Day 2, every 21 days. The primary end point was a response after three cycles. Patients could then proceed to stem cell transplantation (SCT) or receive up to six treatment cycles. Results: Twenty-seven eligible patients were evaluable for toxicity and response. The median age of the patients was 54 years (range, 18–75 years) and most had diffuse large-cell lymphoma. After 3 cycles, there were 4 complete responses (CR; 15%) and 10 partial responses (PR; 37%). There was an overall response rate (RR) of 52%. The RR after completion of all protocol chemotherapy including SCT was 44% (10 CR, 2 PR). In total 88 cycles of GIDOx, grade 3 and 4 neutropenia occurred in 33% and 16% of cycles, respectively. Grade 3 and 4 thrombocytopenia occurred in 14% and 16% of cycles, respectively. Tow patients (2%) experienced febrile neutropenia. Seven patients (26%) proceeded to SCT. Conclusions: GIDOx is an active salvage regimen in aggressive B-cell NHL and can be administered with acceptable toxicity. No significant financial relationships to disclose.

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