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]

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.

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 (&gt; 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 (&lt; 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.

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.

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.

Updated Efficacy and Safety, and Exploratory Ki-67 Results For The MCL-001 Study Of Lenalidomide In Mantle Cell Lymphoma Patients Who Relapsed Or Were Refractory To Bortezomib

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3057-3057 ◽  
Author(s):  
Andre Goy ◽  
Michael E. Williams ◽  
Sevgi Kalayoglu Besisik ◽  
Johannes Drach ◽  
Radhakrishnan Ramchandren ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Research Funding ◽  
Cell Lymphoma ◽  
High Dose ◽  
Efficacy And Safety ◽  
High Dose Therapy ◽  
Ki 67 ◽  
Mantle Cell ◽  
Heavily Pretreated

Abstract Introduction Patients with mantle cell lymphoma (MCL) typically respond to initial therapy and almost inevitably relapse with frequent chemoresistance over time and poor outcome. Multiple phase II studies have established the efficacy and safety of lenalidomide, an immunomodulatory agent with tumoricidal and antiproliferative properties, in relapsed/refractory MCL. The prospective phase II multicenter MCL-001 “EMERGE” study led to FDA approval of lenalidomide for patients with relapsed/refractory MCL after 2 prior treatments, that included bortezomib. The activity of lenalidomide was seen regardless of MIPI, number of prior therapies, prior high dose therapy, bulky disease or high tumor burden. One of the most established prognostic factors in MCL is the proliferation index Ki67 (MIB1), now confirmed both in standard and dose-intensive high-dose therapy strategies. We present here longer follow-up of efficacy and safety from the MCL-001 study in patients relapsed/refractory to bortezomib and the potential relationship between Ki-67 and efficacy outcomes. Methods Patients with heavily pretreated MCL, that included prior bortezomib, received lenalidomide 25 mg/day PO, days 1-21 in 28-day cycles until disease progression or intolerability. Primary study endpoints were overall response rate (ORR) and duration of response (DOR); secondary endpoints included complete response (CR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and safety. Response rates and time-to-event data were analyzed by independent central reviewers per modified IWG criteria and Kaplan-Meier estimates respectively (data cut-off March 20, 2013). Ki-67 was examined as an exploratory endpoint by immunohistochemistry for 81/134 patients (60%) either performed on biopsy samples for 24 patients, or based on the Ki-67 scores reported in local pathology reports for 57 patients. Results Median age for the enrolled intent-to-treat patient population (N=134) was 67 years (range, 43-83; 63% ≥65 years). The median number of previous therapies was 4 (range, 2-10; 78% received ≥3), 93% stage III/IV, and 72% were <6 months from last prior treatment. At a median follow-up of 13.2 months, the ORR was 28% (CR/CRu 8%), with a median DOR of 16.6 months (95% CI, 9.2-26.7; median not reached in patients with CR/CRu) by central review. Median TTR was 2.3 months (95% CI, 1.7-13.1), with a median time to CR/CRu of 4.1 months (95% CI, 1.9-13.2). Median PFS was 4.0 months (95% CI, 3.6-6.9), and median OS was 20.9 months (95% CI, 13.7-24.4). The average dose intensity of lenalidomide was 20 mg/day, for a median duration of 94.5 days (range, 1-1,256). Dose reductions or interruptions due to adverse events (AEs) occurred in 40% and 58% of patients, respectively. Neutropenia (44%), thrombocytopenia (28%), and anemia (11%) were the most common treatment-related grade 3/4 AEs. Ki-67 results were available in 81/134 patients, and efficacy data were categorized using 30% and 50% cut-off thresholds for Ki-67 expression (Table 1). Although patient numbers were limited, the ORR was similar in both lower and higher Ki-67 group, but those with lower Ki-67 levels demonstrated better CR rates, DOR and survival outcomes compared with patients with elevated Ki-67. Conclusions Single-agent lenalidomide in heavily pretreated patients with relapsed/refractory MCL post-bortezomib showed durable long-term efficacy with a consistent safety profile. Consistent with what is reported in the literature, high Ki-67 is associated with poor outcome in our cohort with shorter OS. Though based on retrospective evaluation and subsets of patients, the ORR to lenalidomide was similar in both low and high Ki-67 groups, suggesting lenalidomide can be active in patients expressing high levels of Ki67. Prospective studies are needed to confirm these findings. Disclosures: Goy: Celgene: Consultancy, Research Funding, Speakers Bureau. Off Label Use: This is a phase 2 clinical study of safety and efficacy for lenalidomide in patients with MCL. Williams:Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Drach:Celgene: Honoraria. Ramchandren:Celgene: Research Funding. Zhang:Celgene: Employment. Cicero:Celgene: Employment. Fu:Celgene: Employment. Heise:Celgene: Employment, Equity Ownership. Witzig:Celgene: Research Funding.

Daily Alternating of Immunomodulating Agents and Rituximab in Therapy for Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma: The THRIL (Thalidomide [TH], Rituximab [RI], and Lenalidomide [L]) Regimen

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4203-4203
Author(s):  
Morton Coleman ◽  
Peter Martin ◽  
Jia Ruan ◽  
Ruben Niesvizky ◽  
John P. Leonard ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Adverse Events ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Synergistic Activity ◽  
Small Lymphocytic Lymphoma ◽  
Color Flow ◽  
Mantle Cell ◽  
Continuous Use

Abstract Introduction: Immunomodulatory drugs thalidomide and lenalidomide, alone or in combination with other agents, have shown activity in treatment of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL). Lenalidomide when used as part of the 21 day on, 7 day off schedule, may be limited by marrow toxicity, whereas continuous use of thalidomide is often limited by neurologic toxicity. Interestingly, lenalidomide is not associated with neurologic toxicity, and thalidomide is not associated with marrow toxicity. By alternating thalidomide and lenalidomide daily, adverse events seen with each drug may be attenuated, as total dosage of either drug is reduced. Preliminary data suggest that thalidomide and lenalidomide are not cross-resistant. The two agents may have synergistic activity, resulting in improved responses. This phase II study aims to assess efficacy and safety of THRIL (thalidomide [TH] rituximab [RI], and lenalidomide [L]) combination therapy in patients with CLL/SLL, or MCL. Methods: Patients were treated with the THRIL regimen, which consists of a 50 mg/day thalidomide oral dose, alternated with oral lenalidomide 10 mg/day. Rituximab 375 mg/m2/week was given intravenously for 4 weeks, every 6 months, for up to 4 courses. Patients received 162 mg/day aspirin prophylaxis against venous thromboembolism. Results: Of the 14 patients enrolled, 11 had CLL/SLL, and 3 had MCL; most had received at least 3 prior treatments. Median patient age was 71 years (range 58–9). Four patients had a complete response (CR) as seen by 4-color flow cytometry (n = 2) or bone marrow/computed tomography criteria (n = 2). Three patients had a partial response, and 3 had stable disease. With a median follow-up of 8 months (range 2–27), the median response duration was over 12 months (range 3–27+). The 2 patients with MCL who had a CR, relapsed after 6 and 9 months of therapy, respectively. Disease regressed with increased dosing to 100 mg/day thalidomide and 25 mg/day lenalidomide. Treatment was discontinued in 8 patients due to lack of response (n = 4), progressive disease (n = 2, including 1 patient who initially responded), and rash (n = 2). The THRIL regimen was associated with few adverse events; the only grade 3–4 adverse events were neutropenia and rash, each occurring in 2 patients. Four grade 2 tumor flare reactions were recorded, all in CLL patients, and each successfully treated with steroids. In each case the flares announced a response. No significant neurological adverse events or thromboembolic events were observed. Lenalidomide therapy was paused briefly due to cytopenias in 4 cases. Conclusion: Alternating thalidomide and lenalidomide in the THRIL regimen may be an effective method of reducing adverse events, while achieving responses in patients by enabling longer continuous use of immunomodulating agents. Further investigation is needed to assess whether enhanced responsiveness results from combined sequential use of thalidomide and lenalidomide. Exploration of this regimen may be beneficial in other diseases that respond to lenalidomide and thalidomide, particularly myeloma and myelodysplasia.

Immunochemotherapy As Induction (R-CHOP and R-HyperC-VAD/R-MA) in Mantle Cell Lymphoma, a Hungarian Multicenter Open Label Phase II Study (Rituximab [MabThera®] in Mantle Cell Lymphoma, REMENY)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4889-4889
Author(s):  
Miklos Udvardy ◽  
Andras Rosta ◽  
Zoltan Gasztonyi ◽  
Zita Borbenyi ◽  
Gaspar Radvanyi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Septic Complication ◽  
High Dose ◽  
Open Label ◽  
Number Of Patients ◽  
Mantle Cell ◽  
Initial Staging

Abstract Abstract 4889 Background: Considering the especially poor outcome of mantle cell lymphoma with traditional induction chemotherapies, the Hungarian working group initiated a Hungarian Mantle Cell Lymphoma Study (REMENY) using rituximab (MabThera) based immunochemotherapy. The structure of the trial: National, multicenter, open label trial rituximab based immunochemotherapy induction in mantle cell lymphoma. Two therapies were available according to investigators' choice: R-CHOP-21 (8x) or R-HyperC-VAD/R-MA according to the MD Anderson protocol. High dose therapy + autologous stem cell support (ASCT) was allowed, according to the investigators decision. Diagnosis was based upon standard histology. Initial staging included the standard protocols, imaging techniques, bone marrow evaluation and gastrointestinal endoscopy (not compulsory at initial staging). Recruitment period was planned to be 3 years, the follow-up 2 years. Remission was evaluated according to Cheson (IWC) criteria,CR was qualified only after completion of gastroscopy and colonoscopy, which did not reveal any mantle cell related abnormality. In some cases FDG PET-CT was allowed to substitute for endoscopy. Primary endpoints: OS and PFS, safety Results: Recruitment started in June 2007 and completed unexpectedly early (Nov 2008). 48 patients were included, per protocol Patients were 31 (64.58%), follow-up (24 months) was completed for 15 (31.25%) patients. Ann Arbor III-IV B 43 (89.58%) was dominant. Median PFS for all patients was 30.4 months (SD 5.839, 95% CI: 19–41.9). PFS median for those patients who reached a CR has not been reached while it was 23.7 months in PR (p=0.031). Safety: One hundred-thirteen adverse events occurred in 31 (64.58%) patients; 53 serious adverse events in 15 (31.25%) patients: 17 cytopenia, including fever with neutropenia 7, transient bronchospasm during rituximab (MabThera) infusion 1, hyperglycemia 1 which may be treatment related. There were 20 death cases, 13 of them due to progression of disease, two due to septic complication, three heart failures and one second malignancy (breast cancer). Significantly more patients on the R-HyperC-VAD/R-MA arm experienced adverse events (11/12 patients, 91.6%) compared to R-CHOP (20/36, 55.5%, p=0.035). Conclusion: This trial further confirmed the value of adding rituximab to standard induction therapies in mantle cell lymphoma. The results are conforming to data published in literature. Higher percentage of patients completed R-CHOP regimen. R-HyperC-VAD/R-MA was more effective in inducing CR, but could be completed only in one third of patients. However, in those patients who adhered to R-HyperC-VAD/R-MA therapy, it resulted in 80% CR, vs. 42.3% in the R-CHOP group. This difference is not statistically significant (p=0.172) possibly due to low case numbers. Those patients who reached CR had significantly longer PFS. PFS obtained in this trial is comparable to international data, and could be further improved by adding immunotherapy maintenance. Planned total number of patients (48) entered the trial during the first 12 months. This was surprising, as the expected number of mantle cell lymphoma based on the international incidence data is cca. 30–35 yearly. The unexpectedly high patient numbers need further explanation. Disclosures: Off Label Use: Rituximab is not authorized for Mantle Cell Lymphoma in Hungary.

Impact Of Autologous Stem Cell Transplantation In Older Patients With Mantle Cell Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3384-3384
Author(s):  
Zachary Frosch ◽  
Marlise R. Luskin ◽  
Daniel J. Landsburg ◽  
Stephen J. Schuster ◽  
Jakub Svoboda ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Mantle Cell Lymphoma ◽  
Patient Preference ◽  
Older Patients ◽  
Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Mantle Cell ◽  
Age Over 60

Abstract Background Mantle cell lymphoma (MCL) is a disease of older adults with median age at diagnosis of over 60. While receipt of high-dose chemotherapy with autologous stem cell transplant (ASCT) consolidation has been shown to improve progression free survival (PFS) following standard induction chemo-immunotherapy in younger patients, the benefit of ASCT consolidation in older patients remains uncertain. To address this, we evaluated the benefit of ASCT in a cohort of older patients with MCL treated at our center. Methods Patients age over 60 diagnosed with MCL and treated at the University of Pennsylvania between January 2003 and June 2012 treated with R-CHOP or R-HyperCVAD induction and deemed fit for ASCT at the completion of induction were analyzed. Induction regimen was chosen based on treating physician and/or patient preference. PFS was defined as time from initiation of therapy to radiographic or biopsy proven progression or death in remission, and overall survival (OS) was defined as time from diagnosis to death from any cause. Response assessments were performed at the discretion of the treating physician. Results Thirty-eight patients were identified: 20 (53%) received R-CHOP induction and 18 (47%) received R-HyperCVAD. Baseline patient and disease-related characteristics were similar between groups (Table 1). With R-CHOP, patients received a median of 6 cycles of chemotherapy including mobilization (range 6 to 8). With R-HCVAD, patients received a median of 8 (A or B) cycles including mobilization (range 5 to 8). Adverse events requiring hospitalization or a change in dose or timing of therapy occurred in 67% of R-CHOP and 84% of R-HyperCVAD patients (p=0.27). The most common adverse event was neutropenic fever/infection (15 patients). Significantly more patients undergoing R-HyperCVAD induction required red cell or platelet support (17 [100%] vs 9 [64%], p=0.012). Thirteen patients (72%) completed all cycles of R-HyperCVAD. Three patients (16%) were converted to R-CHOP because of toxicity. Patients who completed at least cycle 2B were included in the R-HyperCVAD group for analysis. Complete response was achieved in all but one patient in each induction group. After R-CHOP induction, 15 (75%) patients underwent ASCT. After R-HyperCVAD, 6 (33%) patients underwent ASCT. The most common reasons for not undergoing ASCT were physician recommendation (6 patients, 35%) and patient preference (5, 29%). Rates of adverse events were similar during ASCT after R-CHOP (9, 60%) or R-HyperCVAD (3, 50%). There was no ASCT associated mortality. Among those not transplanted, after R-HyperCVAD 6 (50%) received rituximab maintenance and none did after R-CHOP. With a median length of follow-up of 2.7 years, median PFS was 2.6 years and median OS was 6.0 years. Kaplan-Meier plots for PFS are shown in Figure 1. Patients treated with R-CHOP+ASCT and R-HyperCVAD alone both had longer PFS than patients treated with R-CHOP alone (median PFS 3.2 vs 1.6 years, p=0.019 and 4.0 vs 1.6 years, p=0.009 respectively). Patients undergoing R-CHOP + ASCT had similar PFS compared to R-HyperCVAD alone (p=0.525). No significant differences in OS survival were found (Figure 2). Conclusion Among patients age over 60 eligible for ASCT in primary MCL, ASCT prolonged PFS after R-CHOP induction and resulted in similar PFS to that seen with R-HyperCVAD. Our results suggest that fit older patients with MCL benefit from chemotherapy with either R-CHOP+ASCT or R-HyperCVAD, and that the former regimen may be preferable due to lower rates of toxicity and need for transfusion support. These findings should be confirmed prospectively. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Mantle Cell Lymphoma Contamination of Autologous Stem Cell Grafts on Outcome After High-Dose Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2558
Author(s):  
Malte Roerden ◽  
Stefan Wirths ◽  
Martin Sökler ◽  
Wolfgang A. Bethge ◽  
Wichard Vogel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Clinical Decision Making ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Mantle Cell ◽  
Autologous Grafts

Novel predictive factors are needed to identify mantle cell lymphoma (MCL) patients at increased risk for relapse after high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDCT/Auto-HSCT). Although bone marrow and peripheral blood involvement is commonly observed in MCL and lymphoma cell contamination of autologous stem cell grafts might facilitate relapse after Auto-HSCT, prevalence and prognostic significance of residual MCL cells in autologous grafts are unknown. We therefore performed a multiparameter flow cytometry (MFC)-based measurable residual disease (MRD) assessment in autologous stem cell grafts and analyzed its association with clinical outcome in an unselected retrospective cohort of 36 MCL patients. MRD was detectable in four (11%) autologous grafts, with MRD levels ranging from 0.002% to 0.2%. Positive graft-MRD was associated with a significantly shorter progression-free and overall survival when compared to graft-MRD negative patients (median 9 vs. 56 months and 25 vs. 132 months, respectively) and predicted early relapse after Auto-HSCT (median time to relapse 9 vs. 44 months). As a predictor of outcome after HDCT/Auto-HSCT, MFC-based assessment of graft-MRD might improve risk stratification and support clinical decision making for risk-oriented treatment strategies in MCL.

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