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.

Anti-tumor activity of mTOR inhibitor temsirolimus for relapsed mantle cell lymphoma: A phase II trial in the North Central Cancer Treatment Group

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7532-7532 ◽  
Author(s):  
S. M. Ansell ◽  
S. M. Geyer ◽  
P. J. Kurtin ◽  
D. J. Inwards ◽  
S. H. Kaufmann ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Early Evaluation ◽  
Overall Response ◽  
Mantle Cell ◽  
Anti Tumor Activity

7532 Background: Mantle Cell Lymphoma (MCL) is characterized by t(11;14) resulting in over expression of cyclin D1, a member of the phosphatidylinosital 3-kinase (PI3K) pathway. Temsirolimus is a novel inhibitor of the mammalian target of rapamycin (mTOR) kinase. Previous studies with weekly temsirolimus at a dose of 250mg demonstrated a 38% overall response rate in 35 patients (JCO 23 (23); 5347–56, 2005). Thrombocytopenia was frequently observed and was dose limiting. The current study tested whether low-doses (25mg) of temsirolimus could produce a similar overall response rate (ORR) with less toxicity. Methods: Eligible patients had biopsy proven cyclin D1 positive MCL and had relapsed or were refractory to therapy. Patients received temsirolimus 25mg IV weekly as a single agent. Patients were restaged after 1 cycle (4 doses), after 3 cycles, and every 3 cycles thereafter. Patients with a tumor response after 6 cycles were eligible to continue drug for a total of 12 or 2 cycles after complete remission (CR) and then were observed without maintenance. The goal was to achieve an ORR of at least 20%. Results: Twenty-nine patients were enrolled between March and August 2005. Twenty-two patients have completed therapy. One patient with a major protocol violation on cycle-1 and one ineligible patient were excluded, leaving 27 evaluable patients. The ORR was 41% (11/27), with 1 CR and 10 PRs. Early evaluation of TTP showed a median of 5.5 months (95% CI: 3.3–7.7) and the duration of response for the 11 responders was 6.2 months (95% CI: 3.6 to not yet reached). These results compare favorably with the 6.5 months and 6.9 months, respectively, found in previous trials that used 250 mg. The median dose delivered per month was 80 mg (range, 10–100 mg). Sixteen (59%) of patients required a dose reduction. The median time on treatment was 4.4 months (95% CI, 3.3–7.7). The incidence of grade 3 and 4 thrombocytopenia was 12% and 0%, respectively. One patient experienced grade 5 infection without neutropenia, which was considered unrelated to CCI-779. Conclusions: Single agent CCI-779 at a dose of 25mg has anti-tumor activity in relapsed MCL similar to the 250 mg dose. This study indicates that combinations of temsirolimus with other agents should be feasible. [Table: see text]

Marked activity of bortezomib, rituximab, and dexamethasone (BORID) in heavily pretreated patients with mantle cell lymphoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17522-17522 ◽  
Author(s):  
J. Drach ◽  
H. Kaufmann ◽  
O. Pichelmayer ◽  
V. Sagaster ◽  
S. Seidl ◽  
...  
Keyword(s):  
Adverse Events ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Proteasome Inhibitors ◽  
High Dose ◽  
Synergistic Activity ◽  
Mantle Cell ◽  
Heavily Pretreated ◽  
Mucosal Candidiasis ◽  
Line Of Therapy

17522 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. Methods: We have initiated a phase II study in relapsed/chemotherapy refractory MCL to evaluate the activity and safety of B in combination with R and dexamethasone (BORID). 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) with progressive MCL after at least one prior line of therapy (including CHOP or a CHOP-like regimen) are eligible. Results: Up to now, we have enrolled 10 pts (median age, 69 years; range, 48 to 75 years) after a median of 3 lines of prior therapies (range, 1 to 6) including R in 8 pts, high-dose therapy in 3 pts, and thalidomide in 5 pts. Median time between start of frontline therapy and study inclusion was 43 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. Of 8 pts evaluable for efficacy, 7 have achieved a response (3 CR, 4 PR), and 1 pt experienced stable disease. Pts in CR were also negative for disease activity by PET scanning. Skin infiltrates (histologically proven T-cell infiltrates) preceded achievement of CR in 2 pts. 6 of 6 pts are still progression-free at 6 months after treatment initiation. Recruitment of patients is ongoing, and updated results will be presented. Conclusions: Data obtained thus far indicate that BORID has promising activitiy and managable toxicity in patients with heavily pretreated MCL, and development of a vasculitic rash may be an early indicator of a favorable response. [Table: see text]

Phase II: Combination of cladribine, cyclophosphamide, mitoxantrone, rituximab (R-CCM) in patients with relapsed and refractory follicular and mantle cell lymphoma, results of a prospective study at Kitasato University

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18542-18542 ◽  
Author(s):  
Y. Suzuki ◽  
M. Danbara ◽  
M. Hayama ◽  
T. Togano ◽  
M. Ohsaka ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Hemorrhagic Cystitis ◽  
Single Agent ◽  
Left Ventricular ◽  
Overall Response ◽  
Mantle Cell ◽  
Grade Iii

18542 Background: Indolent non-Hodgkin’s lymphoma (I-NHL) account for 20% of all of NHL in Japan, and they are increasing in number. More than 80% of the patients who achieve a complete remission with the initial treatment, will require salvage therapy. Recently, cladribine (2-CdA), a purine analogue is receiving much attention, because, even as a single agent, it has shown a high efficacy for I-NHL. The aim of our study was to determine the effectiveness and toxicity of combined chemotherapy consisting of 2-CdA, cyclophosphamide (CYP), mitoxantrone (MIT), rituximab (R-CCM) in the treatment of refractory or relapsed I-NHL. Methods: Patient eligibility criteria were: Previously treated patients with I-NHL, refractory or relapsed disease, no chemotherapy or irradiation within 4 weeks prior to the study, life expectancy of at least 3 months, age: 20–75, perfomance status of 0–3, adequate function ( bone marrow, liver, kidney, lung, heart) and written informed consent. The treatment regimen was: 2-CdA given at a dose of 0.09 mg/kg/day in a 2-h intravenous infusion from day 2–4, CYP 200 mg/m2/day from day 2–4, MIT 8 mg/m2/day on day 2 and rituximab 375 mg/m2/day on day .Primary end point was overall response rate. Results: 9 patients were enrolled, 7 (2 with mantle cell lymphoma, MCL; and 5 with follicular lymphoma, FL) were eligible. Mean Age was 63(51–72). The mean observation time was 121 days(47–314). Overall response rate (complete and partial) just after this therapy was 85.7%, one was progressive disease. One of PR one relapsed and died ten months after this regimen. The major toxicity was myelosuppression. Grade-III and -IV neutropenia was seen in 7 patients, grade-III thrombocytopenia in one and grade-III hemorrhagic cystitis in one, but all of them recovered from these toxicity. After the treatment, Grade-IV pneumonia and grade-III left-ventricular diastolic dysfunction was seen in the PD patient and passed away. Conclusions: the R-CCM is effective and safe in a combined regimen for relapsed and refractory I-NHL patients. We have just begun this new regimen, therefore, further investigations with larger population are warranted. No significant financial relationships to disclose.

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.

Promising Activity of Bortezomib, Rituximab, and Dexamethason (BORID) in Patients with Relapsed Mantle Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4799-4799
Author(s):  
Johannes Drach ◽  
Sonja Seidl ◽  
Oskar Pichelmayer ◽  
Hannes Kaufmann ◽  
Christoph Zielinski ◽  
...  
Keyword(s):  
Adverse Events ◽  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
Autologous Transplantation ◽  
High Dose ◽  
Synergistic Activity ◽  
Phase Ii Studies ◽  
Mantle Cell

Abstract Bortezomib (B) belongs to a new class of anti-cancer agents, the proteasome inhibitors, and has documented activity in multiple myeloma. Moreover, recent data indicate that B is also effective in other B-cell malignancies, most notably in mantle cell lymphoma (MCL). Phase II studies revealed remission rates between 40 and 55% of patients with relapsed or refractory MCL. Preclinical studies suggest that B has synergistic activity with rituximab (R), which provides a rationale for the exploration of such a treatment combination. We have therefore initiated a phase II study in relapsed/chemotherapy refractory MCL in order to evaluate the activity and safety of B in combination with R and dexamethasone (BORID). 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 with progressive MCL after at least one prior line of therapy (including CHOP or a CHOP-like regimen) are eligible. Up to now, we have enrolled 7 patients at a median age of 65 years (range, 52 to 74 years); they had received one to 6 lines of prior therapy including R in 5 of them and high-dose chemotherapy followed by autologous stem cell transplantation in 2 patients. Severe adverse events (&gt; grade II) included 3 infections (herpes zoster, bacterial pneumonia, pneumonia of potential viral origin), grade III peripheral neuropathy in one patient, and nodular skin infiltrates in one patient. All adverse events were managable by standard means of supportive care and prolongation of the treatment interval between cycles. No severe hematological toxicity has yet been encountered. Of 6 patients evaluable for efficacy, 5 have achieved a response (1 CR, 4 PR), and 1 patient experienced stable disease. The patient in CR (previously treated by R-CHOP, autologous transplantation, and R plus thalidomide) was also negative for disease activity by PET scanning. None of the patients has yet progressed at 4 to 9 months after initiation of BORID. Recruitment of patients is ongoing, and updated results will be presented. Data obtained thus far indicate that BORID has promising activitiy and managable toxicity in patients with relapsed MCL, which warrants further investigation not only in MCL but also in other B-cell lymphomas.

Ibrutinib With Rituximab in First-Line Treatment of Older Patients With Mantle Cell Lymphoma

2021 ◽  
Author(s):  
Preetesh Jain ◽  
Shuangtao Zhao ◽  
Hun Ju Lee ◽  
Holly A. Hill ◽  
Chi Young Ok ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Older Patients ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Complete Response ◽  
Ki 67 ◽  
Overall Response ◽  
Mantle Cell ◽  
Grade 3

PURPOSE Most patients with mantle cell lymphoma (MCL) are older. In this study, we investigated the efficacy and safety of a chemotherapy-free combination with ibrutinib and rituximab (IR) in previously untreated older patients with MCL (age ≥ 65 years). METHODS We enrolled 50 patients with MCL in this single-institution, single-arm, phase II clinical trial ( NCT01880567 ). Patients with Ki-67% ≥ 50% and blastoid morphology were excluded. Ibrutinib was administered with rituximab up to 2 years with continuation of ibrutinib alone. The primary objective was to assess the overall response rate and safety of IR. In evaluable samples, whole-exome sequencing and bulk RNA sequencing from baseline tissue samples were performed. RESULTS The median age was 71 years (interquartile range 69-76 years). Sixteen percent of patients had high-risk simplified MCL international prognostic index. The Ki-67% was low (< 30%) in 38 (76%) and moderately high (≥ 30%-50%) in 12 (24%) patients. The best overall response rate was 96% (71% complete response). After a median follow-up of 45 months (interquartile range 24-56 months), 28 (56%) patients came off study for various reasons (including four progression, 21 toxicities, and three miscellaneous reasons). The median progression-free survival and overall survival were not reached, and 3-year survival was 87% and 94%, respectively. None of the patients died on study therapy. Notably, 11 (22%) patients had grade 3 atrial fibrillation. Grade 3-4 myelosuppression was seen in < 5% of patients. Differential overexpression of CCND1, BIRC3, BANK1, SETBP1, AXIN2, and IL2RA was noted in partial responders compared with patients with complete response. CONCLUSION IR combination is effective in older patients with MCL. Baseline evaluation for cardiovascular risks is highly recommended. Randomized trial is needed for definitive conclusions.

Marked Activity of Bortezomib, Rituximab, and Dexamethason in Relapsed and Refractory Mantle Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2753-2753 ◽  
Author(s):  
Johannes Drach ◽  
Hannes Kaufmann ◽  
Oskar Pichelmayer ◽  
Verena Sagaster ◽  
Sonja Seidl ◽  
...  
Keyword(s):  
Adverse Events ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
High Dose ◽  
Synergistic Activity ◽  
Durable Response ◽  
Mantle Cell ◽  
Line Of Therapy

Abstract 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 have initiated a phase II study in relapsed/chemotherapy refractory MCL to evaluate the activity and safety of B in combination with R and dexamethasone (BORID). 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) with progressive MCL after at least one prior line of therapy (including CHOP or a CHOP-like regimen) are eligible. We have now enrolled 14 pts at a median age of 69 years (range, 48 to 75 years) after a median of 3 lines of prior therapies (range, 1 to 6) including R in 12 pts, high-dose therapy in 4 pts, and thalidomide in 7 pts. Median time between start of frontline therapy and study inclusion was 43 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), vasculitic skin infiltrates in 3 pts, and hyponatremia in 1 pt. 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. Of 12 pts evaluable for efficacy, 9 have achieved a response (3 CR, 6 PR), and 2 pts experienced stable disease. Pts in CR were also negative for disease activity by PET scanning. Skin infiltrates (histologically proven T-cell infiltrates) preceded achievement of CR in 2 pts. All 3 pts who achieved a CR are still progression-free at 12 months after treatment initiation. Among pts in PR, 3 pts have relapsed (progression-free survival 14, 11, and 6 months, respectively), and 3 pts are still progression-free beyond 6 months from initiation of treatment. In summary, the BORID treatment regimen has promising activitiy and managable toxicity in patients with heavily pretreated MCL, and development of a vasculitic rash may be an early indicator of a favorable and durable response.

scholarly journals The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma

Blood ◽  
2011 ◽  
Vol 117 (10) ◽  
pp. 2807-2812 ◽  
Author(s):  
Jonathan W. Friedberg ◽  
Julie M. Vose ◽  
Jennifer L. Kelly ◽  
Faith Young ◽  
Steven H. Bernstein ◽  
...  
Keyword(s):  
Adverse Events ◽  
Mantle Cell Lymphoma ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Objective Response ◽  
Synergistic Activity ◽  
Significant Activity ◽  
Serious Adverse Events ◽  
Non Hodgkin Lymphoma ◽  
Mantle Cell

AbstractGiven the significant activity and tolerability of bendamustine, rituximab, and bortezomib in patients with relapsed indolent and mantle cell non-Hodgkin lymphoma, and laboratory studies suggesting synergistic activity, we conducted a multicenter phase 2 study of the bendamustine/bortezomib/rituximab combination. Patients with relapsed or refractory indolent and mantle cell lymphoma with adequate organ function were treated with bendamustine 90 mg/m2 days 1 and 4; rituximab 375 mg/m2 day 1, and bortezomib 1.3 mg/m2 days 1, 4, 8, 11. Six 28-day cycles were planned. Thirty patients (7 with mantle cell lymphoma) were enrolled and treated. Eight patients experienced serious adverse events, including one event of grade 5 sepsis. Common nonhematologic adverse events were generally grade 1 or grade 2 and included nausea (50%), neuropathy (47%), fatigue (47%), constipation (40%), and fever (40%). Of 29 patients evaluable for efficacy, 24 (83%) achieved an objective response (including 15 with complete response). With median follow-up of 24 months, 2-year progression-free survival is 47% (95% confidence interval, 25%-69%). On the basis of these promising results, the US cooperative groups have initiated randomized trials to evaluate this regimen in follicular and mantle cell lymphoma. This trial was registered at www.clinicaltrials.gov as #NCT00547534.

Multimodal Dose Dense Therapy for Mantle Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1163-1163
Author(s):  
Sam O. Wanko ◽  
Jon P. Gocherman ◽  
Joseph O. Moore ◽  
Carlos Decastro ◽  
Robert Prosnitz ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Induction Therapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Mantle Cell ◽  
Dose Dense

Abstract BACKGROUND: Mantle cell lymphoma (MCL) typically has a poor outcome with overall survival of only 3–4 years. Higher treatment response and event-free survival has been demonstrated with aggressive high dose chemotherapy followed by autologous hematopoietic stem cell support, though long term cure rates remain unclear(Dreger P. Hematol J. 2000;vol.2). Modest response rates have also been reported with the monoclonal antibody (MoAb) rituximab and ALEMTUZUMAB (Foran, JM. JCO 2000; vol. 2. Faderl S. Blood 2003; vol. 9). We therefore combined dose-dense therapy with MoAbs to explore response rate and event free survival (EFS) in mantle cell lymphoma. The strength of this trial design is ability to follow all patients from induction chemotherapy through high dose therapy and transplant in order to gauge clinical outcome on all enrolled patients, not just the subpopulation who is able to proceed to high dose therapy. PATIENTS AND METHODS: Induction therapy consisted of 1 cycle of high dose cytarabine (3gm/m2 IV over 1 hour Q12H for 8 doses), mitoxantrone (10mg/m2 daily for 3 days), and ALEMTUZUMAB 30mg IV 3 times a week for 6 weeks with growth factor support. All responding patients were mobilized with cyclophosphamide 4gm/m2 and G-CSF 10 mcg/kg/day and/or bone marrow harvest. The transplant preparative regimen was carmustine 15mg/kg over 2 hours day -6, etoposide 60mg/kg over 4 hours day -4, and cyclophosphamide 100mg/kg over 2 hours day -2 followed by autologous reinfusion on day zero. Consolidation was given with rituximab 375mg/m2 weekly for 4 doses at 6 weeks and 6 months post transplant. RESULT: 9 patients with advanced disease (7 stage IV, 1 stage III, 1 stage IIA) and median age of 60 (48 – 65 years) have been accrued and treated since February 2003. Four were newly diagnosed and 5 had relapsed/refractory disease. Seventy eight percent (7/9) had complete response and 22% (2/9) had partial response (PR) following induction therapy. One patient had severe infection after induction and was unable to proceed to transplant. Another had constitutional decline preventing further therapy and each died within 4 months of withdrawal from the protocol. Both had relapse/refractory disease at accrual. The remaining 7 patients proceeded to the transplant phase. With a median follow-up of 7 months (range 3–16 months), all 7 patients remain in CR for 1 –16 months. Significant induction therapy toxicity included neutropenia in all 9 patients with average duration of 10.7 days, non-disseminated CMV reactivation in 44% of patients, one overwhelming fungal infection, and one patient with delay in engraftment. Figure Figure CONCLUSION: Our preliminary data show a high induction and transplant phase completion rate, manageable toxicity, and excellent overall response rate in this group of elderly patients with advanced disease. Larger numbers of patients and longer follow-up is needed to confirm these promising results.

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