In Vivo Purging with Hyper-CVAD Plus Rituximab Followed by Autologous Stem Cells Transplant and Rituximab Maintenance in Newly Diagnosed Mantle Cell Lymphoma: A Pilot Study for GISL (Italian Cooperative Study Group for Lymphoma).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5494-5494
Author(s):  
Edoardo Benedetti ◽  
Francesco Caracciolo ◽  
Sara Galimberti ◽  
Federico Papineschi ◽  
Matteo Pelosini ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Dose Intensity ◽  
High Dose ◽  
Cell Transplant ◽  
Rituximab Maintenance ◽  
Mantle Cell ◽  
High Dose Intensity

Abstract Previously untreated mantle cell lymphoma (MCL) are consistently associated with poor prognosis when treated with CHOP-like regimens. Typically the CR rate is 20–30%, median FFS = 10–16 months and median OS = 3 years. In the attempt to improve outcome we used a high dose intensity regimen such as Hyper-CVAD (HCVAD) with autologous stem cell transplant (ASCT). Twenty patients entered the study but only 10 up to now are valuable. Patients were apheresed after 2nd course of HCVAD and if apheresis (LPH) were PCR positive (Bcl1+/JH+) a second set of LPH were performed after completion of 4th cycle. To perform an in vivo purging Rituximab 375 mg/m2 was added at day +1 and +9 after last dose of ARA-C; GCSF 10μg/kg was commenced on day +5 until LPH was ultimated. Rituximab maintenance (375 mg/m2 once weekly for 4 consecutive weeks) started 2 month post-ASCT and was repeated every 6 months. Ten patients have completed 4 HCVAD and 7 /10 underwent ASCT and were conditioned with BEAM. After 4 HCVAD 7/10 patients were in CR and 3/7 in PR. After ASCT 1 PR obtained a CR, 1 PD obtained a VGPR and 5 CR maintained CR. Only 4CR post ASCT have received Rituximab maintenance and maintain CR. Two patients (1 CR blastic variant and 1 PR) refused ASCT and after 4 HCVAD received Rituximab maintenance and both are in CCR. Overall with a median follow up of 28.6 months (range 12–51) median survival is not reached. At 4 years 77.8% of patients are alive and PFS is 87.9%. Patients were monitored for bone marrow-MRD by PCR. Eight out of 10 were PCR+ at diagnosis and 7/8 were PCR negative after 4 HCVAD. After ASCT one PCR+ converted to PCR- and 1 PCR+ patient after 4 HCVAD converted to PCR- with Rituximab maintenance (refused ASCT). Conclusions: high dose intensity regimen HCVAD + Rituximab as in vivo purging and for maintenance allowed to collect tumor free grafts in 70% of PCR+patients at diagnosis and to reach an ORR of 100%, 7/10 CR and PR 3/10 (included 1 blastic variant). PCR negativity was obtained in 7/8 patients. One patient from PR converted to CR after ASCT and one after Rituximab maintenance (without ASCT); thus we might speculate that both high doses (BEAM) and Rituximab do play a role to increase the probability to obtain a CR and PCR-. Survival and PFS of 77.8% and 87.9% respectively at 4 years are encouraging. Further follow up and a higher enrolment of patients are needed to better define the role of HCVAD + Rituximab and ASCT to increase CR,PCR- PFS and OS in MCL.

Prolongation of Progression Free Survival In Mantle Cell Lymphoma After RHCVAD: ASCT Consolidation or Rituximab Maintenance

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3570-3570
Author(s):  
Jennifer McQuade ◽  
Tahamtan Ahmadi ◽  
David Porter ◽  
Noelle Frey ◽  
Alison Wakoff Loren ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Primary Study ◽  
Cell Transplant ◽  
Data Set ◽  
Bulky Disease ◽  
Rituximab Maintenance ◽  
Mantle Cell

Abstract Abstract 3570 Mantle cell lymphoma (MCL) is a small B cell lymphoma, incurable with standard chemo-immunotherapy. The best initial treatment regimen remains unclear. Although it is generally acknowledged that aggressive approaches using combination chemotherapy and/or high dose chemotherapy can prolong survival, consensus on upfront treatment strategies for advanced MCL is currently lacking without randomized controlled data to guide treatment decisions. We conducted a retrospective cohort analysis to describe and compare the survival experiences of MCL patients at the University of Pennsylvania treated in the first-line setting with R-HCVAD (N=43) with or without autologous stem cell transplant (ASCT) or Rituximab maintenance. The primary study endpoints were PFS and OS as assessed by chart review and confirmed by SSDI database. Median follow up for all pts was 3 years. The median age was 53.7, and 76.7 % (n=33) were stage IV at diagnosis. 15 patients underwent consolidative ASCT. 11 pts received Rituximab maintenance. Comparing patients treated with R-HCVAD vs R-HCVAD + R maintenance vs. R-HCVAD + ASCT, there were no statistical differences in terms of age, ECOG PS, LDH, WBC, beta-2microglobulin, BM or GI involvement, bulky disease or blastoid variant at baseline. Median PFS for all patients was 3.9 years: R-HCVAD alone 2.1 years vs. R-HCVAD+R 3.9 years (P=0.02, HR 3.51, 95%CI: 1.2–10.2) vs R-HCVAD + SCT not reached (p=0.017, HR 3.7, 95%CI: 1.26–10.63). PFS survival rates at 2 years were 50%, 88% and 70%; 33%, 71/% and 63% respectively at 3 years, and 0%, 33% and 33 % at 5 years. 3 year OS for all patients was 84% (95% CI: 65–94) with no significant differences among the three approaches. Notably, only 1/8 patients treated with R-HCVAD + SCT relapsed after 2 years, with a median follow up of 4.8 years for these patients. Our data suggest a further improved PFS when R-HCVAD is consolidated with either Rituximab maintenance or ASCT. While neither of the two consolidative approaches appears superior in our limited data set, both show significant PFS prolongation when compared to R-HCVAD alone. Further prospective investigation of consolidative approaches after RHCVAD in a randomized fashion is warranted. Figure 1: Figure 1:. Disclosures: No relevant conflicts of interest to declare.

Phase II Study of Modified Hyper-CVAD with Rituximab Maintenance for Previously Untreated Mantle Cell Lymphoma: A Wisconsin Oncology Network Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1388-1388 ◽  
Author(s):  
Brad S. Kahl ◽  
James McGovern ◽  
Jules Blank ◽  
Anthony Jaslowski ◽  
Gerald Bayer ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Progressive Disease ◽  
Cell Lymphoma ◽  
Response Rates ◽  
High Response ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Rituximab Maintenance ◽  
Mantle Cell

Abstract Introduction: Mantle cell lymphoma has the poorest 5-year survival of all the non-Hodgkin’s lymphoma subtypes and appears incurable with standard therapies. High response rates are seen with CHOP plus rituximab (R), but the progression free survival (PFS) is disappointingly short (median 16–20 months). Favorable results have been reported for hyper-CVAD + R with midcycle high dose methotrexate and cytarabine, but this regimen can be prohibitively toxic for some patients. We hypothesized that eliminating methotrexate and cytarabine while adding R to the induction hyper-CVAD would produce high response rates with acceptable toxicity. We further hypothesized that adding R maintenance would prolong the PFS. Methods: Eligible patients had histologically confirmed CD20+ mantle cell lymphoma and could not have received more than 1 cycle of CHOP-like therapy for their disease prior to study entry. PS 0-2 was allowed. The treatment plan included rituximab 375 mg/m2 IV day 1, cyclophosphamide 300 mg/m2 IV over 3 hrs q 12 hrs X 6 doses days 1–3, doxorubicin 50 mg/m2 continuous infusion over 48 hrs days 1–2, vincristine 2 mg IV day 3, dexamethasone 40 mg po days 1–4, and G-CSF 5mg/kg/day starting after therapy until ANC ≥ 4000/mm3. Cycles were repeated every 28 days, up to 6 cycles. Patients achieving at least a PR received R maintenance therapy (375 mg/m2 IV weekly X 4 doses) every 6 months for 2 years. The accrual goal was 20 patients evaluable for response. Results: Enrollment is completed. All 22 patients are evaluable for toxicity, PFS, and OS and 20 patients evaluable for response rate (2 patients died before any restaging). Patient characteristics include 20/22 male, median age 63 (40–81), median IPI 3 (1–5), and 19/22 stage IV. All patients have completed the induction chemotherapy. Six patients have completed the R maintenance, 10 remain on R maintenance, and 6 patients came off study due to progressive disease (4) or death (2). The ORR is 85% (17/20) with 3 PR, 14 CR/CRu. With a median follow up of 22.5 months (range 4–45), the median PFS and OS have not been reached. The 2-year PFS is 73% (95% CI 50–89%) and the 2-year OS is 82% (95% CI 60–95%). Responses are ongoing in 16 patients, with response duration ranging from 2+ to 39+ months. The most common grade 3–4 toxicities in the 22 patients included neutropenia (10), anemia (5), thrombocytopenia (5), and infection (4). To date, five patients who participated in this study have died (1 treatment-related neutropenic fever, 1 post-surgical infection, 3 progressive disease). The major toxicity of this treatment regimen is expected hematologic toxicity. Conclusion: Modified hyper-CVAD with rituximab maintenance demonstrates ORR comparable to conventional hyper-CVAD (85% vs. 93%) and is less toxic, especially in patients over 60. Compared with published reports for R-CHOP, we observed higher CR rates (70% vs 34–48%) and considerably longer median PFS (not yet reached vs. 16–20 months). Longer follow up will better define the effectiveness of this regimen, but the encouraging results of this pilot study provide the basis for additional study in a larger setting.

scholarly journals Long Term Follow-up in Mantle Cell Lymphoma Patients Treated with R-GemOx Followed By Consolidation and Rituximab Maintenance

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5337-5337
Author(s):  
Marta Garcia Recio ◽  
Leyre Bento ◽  
Sandra Pérez-León ◽  
Sara Aida Jiménez-Julià ◽  
Jordi Gines ◽  
...  
Keyword(s):  
High Risk ◽  
Mantle Cell Lymphoma ◽  
Therapeutic Approach ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
Age At Diagnosis ◽  
Cell Transplant ◽  
Rituximab Maintenance ◽  
Mantle Cell

Abstract Introduction: Six percent of all non-Hodgkin lymphomas (NHL) cases are mantle cell lymphoma (MCL). MCL has a poor prognosis and is considered incurable with current strategies. Intensive approaches are not applicable to most these patients considering the median age at diagnosis (70 years old). Due to the molecular events that drive MCL to be a lymphoma with an aggressive and indolent behavior as well as a tendency to clonal evolution (dysfunction of cell cycle, response to cellular damage and apoptosis), we present a global therapeutic approach which includes an effective induction with a low toxic profile, as well as consolidation and maintenance with the final aim of increasing and maintaining responses. Methods: From December-2008 to January-2018 all MCL patients treated in first line in our center were included. The therapeutic approach was based on an induction with R-GemOx (rituximab, gemcitabine and oxaliplatin) followed by consolidation with autologous stem cell transplant or ibritumomab tiuxetan followed by rituximab maintenance (Rm) (every 2 months for 2-3 years). Since 2016, all patients with less than complete response after induction/consolidation, received Ibrutinib 560 mg daily added to Rm. Standard prognostic variables were collected at diagnosis including MIPI; the response evaluation and follow-up was made considering Cheson criteria; for toxicity assessment, we used OMS grading scales of toxicity criteria. Overall survival (OS) and progression free survival (PFS) were estimated from the beginning of the treatment with the Kaplan-Meier method. Results: Thirteen treatment-naïve MCL patients were included from December-2008 to January-2018. Main characteristics of patients are shown in Table 1. Briefly, this is an old high risk series with a median age at diagnosis of 71 years old and poor prognosis (31% and 69% belong to intermediate and high risk MIPI groups, respectively). Two cases were refractory to R-GemOx induction (a blastic MCL and another case with high MIPI (7.7)). Four cases relapsed between 30 and 66 months after treatment was started. All cases with CR or PR after induction (n=11; 85%), obtained a CR at the end of the maintenance. One of the refractory cases after a second line followed by rituximab and ibrutinib maintenance also reached CR. Only 2 patients died (15%): one disease progression and another non-related pulmonary thromboembolism. The median follow-up was 51 months. Four-years OS was of 83% with a median PFS of 58 months (Figure 1). R-GemOx toxicity profile was manageable: most of them grade 1-2 neutropenia (43%), vomits (100%), diarrhea (30%) and anemia (30%). Grade 3-4 toxicity was scarce (neutropenia 14% and thrombocytopenia 36%). Conclusions: R-GemOx followed by consolidation and Rm should was an effective approach with manageable toxicity and excellent survival considering the median age and the high MIPI risk of the series. We plan to test this global approach in a prospective clinical trial. Disclosures No relevant conflicts of interest to declare.

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.

Rituximab and Stem Cell Transplantation Produces Durable Remissions in Mantle Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1390-1390
Author(s):  
Francisco J. Capote ◽  
M. J. Pascual ◽  
E. Gonzalez-Barca ◽  
J. M. Bergua ◽  
A. Jimenez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Cell Lymphoma ◽  
High Dose ◽  
Free Survival ◽  
Mantle Cell

Abstract Introduction: Mantle cell lymphoma (MCL) is a CD20+ malignancy comprising up 5% of non-Hodgkin’s lymphomas, and has a poor prognosis under standard chemotherapy. The HyperCVAD-M/A regimen (fractionated high-dose cyclophosphamide, vincristine, doxorubicin and prednisolone alternated with methotraxate and cytarabine) has yielded encouraging results when combined with autologous stem cell transplantation (ASCT) in MCL, with 5-year failure-free survival of 54% and overall survival 72%. In an effort to improve these results further, we have combined rituximab in vivo purging and post-transplant consolidation with HyperCVAD-M/A plus ASCT. Methods: Patients aged <65 years with previously untreated or relapsed MCL were treated with four courses of HyperCVAD-M/A followed by four once-weekly doses of rituximab 375mg/m2 as purging prior to stem cell mobilization and harvesting, high-dose chemotherapy (ICT-CY or BEAM), stem cell reinfusion and four further doses of rituximab immunotherapy post-transplant. Results: Of the 34 patients enrolled so far, 15 (12 male, 3 female; 12 previously untreated) have been transplanted. The median age was 52 years (range 47–63 years). After the final post-ASCT immunotherapy all 15 patients were in clinical complete remission. With a median follow-up of 30 months from diagnosis (range 7–52 months), 14 patients remain alive with 13 in first complete remission. One patient died 15 months post-ASCT without evidence of disease recurrence. Kaplan-Meier estimates of 4-year overall and event-free survival are 93.3% and 86.6% respectively. Conclusions: This approach seems safe and feasible and produces durable remissions; longer follow-up of a more patients will be required to assess the effect of the procedure on survival.

Rituximab Plus Hypercvad Alternating with High Dose Methotrexate and Cytarabine for Patients with Newly Diagnosed Mantle Cell Lymphoma. A Multicenter Trial from GISL

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3050-3050 ◽  
Author(s):  
Francesco Merli ◽  
Stefano Luminari ◽  
Fiorella Ilariucci ◽  
Caterina Stelitano ◽  
Mario Petrini ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Hematological Toxicity ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Dose Methotrexate ◽  
Mantle Cell

Abstract BACKGROUND. Rituximab plus HyperCVAD alternating with High Dose Methotrexate and Cytarabine (R-HCVAD) has been tested in patients with newly diagnosed Mantle Cell Lymphoma (MCL) with promising results (Romaguera et al. JCO 2005). In 2005 the Gruppo Italiano Studio Linfomi (GISL) started a phase II multicenter study investigating clinical activity and toxicity of R-HCVAD in a similar group of patients. PATIENTS AND METHODS. To be included in the trial patients must have histologically confirmed diagnosis of MCL, be younger than 70 years, have adequate organ function. Chemotherapy consisted of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicine, and dexamethasone(considered one cycle) alternating every 21 days with rituximab plus high dose methotrexate-cytarabine (considered one cycle) for a total of eight cycles per the MD Anderson protocol. Patients with baseline PCR positivity for t(11;14) on bone marrow (BM) had to perform PCR assessment of BM at evaluation of response and during follow-up. Only patients achieving partial response (PR) were to be addressed to HDC followed by ASCT. RESULTS. Thirty-two patients were enrolled. There were 23 males and 9 females; median age was 54 yrs (29 to 66), 80% were in stage IV, 50% and 71% had Gastrointestinal (GI) and BM involvement, respectively; PCR for t(11;14) was positive on BM in 51% of cases. Seven patients did not complete treatment due to toxicity; of these, two patients died (one with septic shock at cycle 1, one with pulmonary aspergillosis at cycle 4), one patient had thrombosis of central line extended to right atrium at cycle 1, one had grade IV skin reaction at cycle 3, one had a severe pneumonia at cycle 1, two had persistent grade IV hematological toxicity after cycle 1 and 5, respectively. All patients had grade III–IV hematological toxicity. Response was assessed in 17 patients with 16 CR and 1 PR. PCR for t(11;14) negativity on BM was achieved in 4/9 patients after cycle 4 and in 8/9 after cycle 8. After a median follow-up of 24 months 1 patient progressed at 6 months and 1 patient relapsed after 26 months of follow-up. Two-year Failure Free Survival (FFS) was 75% (IC95% 53 to 87) and 2 year Disease Free Survival was 93%(IC95% 59–99). CONCLUSIONS. Though longer follow-up is needed R-HCVAD regimen used in our multicenter setting confirmed high efficacy in terms of response (both clinical and molecular) and FFS. However the regimen was associated to a severe toxicity profile that caused treatment discontinuation in several patients and that may limit its use in the clinical setting.

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.

scholarly journals Efficacy of Chemotherapeutic Regimens for Mantle Cell Lymphoma: A Systematic Review of Phase III Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Ali Jaan ◽  
Muhammad Tayyeb ◽  
Farhan Khalid ◽  
Muhammad Khawar Sana ◽  
Zahoor Ahmed ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Cell Transplant ◽  
Mantle Cell ◽  
Combination Regimens

Background: The mainstay treatment for mantle cell lymphoma (MCL) is chemotherapy ± immunotherapy. The standard chemotherapeutic regimens have limited efficacy in MCL when used alone. In this systematic review, we have assessed the efficacy and safety of various combination regimens for the treatment of MCL evaluated in phase III clinical trials. Methods: We performed a comprehensive systematic literature search on PubMed, Embase, clinicaltrials.gov, and Web of Science databases with the date of inception to May 2020. We used MeSH (Medical Subject Headings) terms for "mantle cell lymphoma", "treatment outcome" along with their keywords, and combined their results. Our search generated a total of 3572 articles. After excluding case reports, case series, observational studies, review articles, meta-analysis, phase I/II clinical trials, and pre-clinical studies, we included five phase III randomized clinical trials (RCTs) reporting the efficacy of combination regimens for MCL treatment. Results Data from five phase III RCTs was pooled with total N=1683 (newly diagnosed (ND), n=1242, relapsed/refractory (RR), n=441). 1610 patients were evaluable. Kluin-Nelemans et al. 2020 (n=560) studied induction with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) vs R-FC (rituximab, fludarabine, and cyclophosphamide) for ND-MCL with follow-up on maintenance with rituximab (R) -vs interferon alfa. At a median follow up of 7.6 years (y), median overall survival (mOS) was 6.4 vs 3.9 y (p=0.0054) in R-CHOP vs R-FC group, respectively. The median progression-free survival (mPFS) and mOS in the R-CHOP cohort on R maintenance were significantly better when compared to those on interferon alfa maintenance (mPFS, 5.4 y vs 1.9 y, p&lt;0.001) (mOS, 9.8 y vs 7.1 y, p=0.0026). Robak et al. (2015) (n=487) assessed bortezomib in ND-MCL by substituting it for vincristine in the standard R-CHOP therapy. A cohort of MCL ineligible for stem cell transplant (SCT) was randomly assigned to either R-CHOP or VR-CAP (bortezomib replacing vincristine). At a median follow-up of 40 months (mo), mPFS was 24.7 mo vs 14.4 mo in VR-CAP vs R-CHOP (HR 0.63, p&lt;0.001), respectively. Similar, relative improvements were reported in complete response (CR) (53% vs 42%, p=0.007) and 4-year OS was (64% [95% CI 56-71] vs 54% [95% CI 45-62]). Jin et al. (2018) (n=121) assessed R-CHOP vs VR-CAP in ND-MCL patients ineligible for SCT. After a median follow-up of 42.4 mo, mPFS for VR-CAP was better than R-CHOP (28.6 mo vs 13.9 mo, HR=0.7, p=0.157). The overall response rate (ORR) was almost similar in VR-CAP (97%) and R-CHOP (98%). The 4-year OS was 62% vs 61% in VR-CAP vs R-CHOP, respectively. Flinn et al. (2014) (n=74) studied the efficacy of bendamustine in combination with rituximab (BR) vs R-CHOP or R-CVP (R-CHOP minus doxorubicin) as induction regimens in ND-MCL. 36 patients received BR and 38 patients received R-CHOP/R-CVP. ORR was 94% vs 85% with BR vs R-CHOP/R-CVP, respectively. Hess et al. (2009) (n=162) evaluated temsirolimus in RR-MCL. The study population was randomized to either 175/75mg temsirolimus (arm A), 175/25mg temsirolimus (arm B), and the investigator's choice of chemotherapy (arm C). The mPFS was significantly better in arm A compared to arm C (4.8 mo vs 1.9 mo, HR 0.44 [97.5% CI 0.25-0.7], p=0.0009). Arm B had slight improvement but insignificant. Similarly, mOS was 12.8 mo in arm A (HR 0.8 [95% CI 0.5-1.28], p=0.35), and 8.8 in arm B (HR 0.96 [95% CI 0.60-1.54], p=0.87), when compared to 9.5 mo in arm C. Drelying et al. (2016) (n=280), studied temsirolimus in comparison with ibrutinib, RR-MCL with mPFS of 14.6 mo (95% CI 10.4-not estimable) vs 6.2 mo (95% CI 4.2-7.9), respectively. Toxicities were typically manageable. VR-CAP was associated with a higher incidence of toxicity (100%) vs R-CHOP (94%) majority of which was hematological. Thrombocytopenia was particularly more prominent with temsirolimus. Granulocytopenia was persistent in 30-40% in the R-FC cohort after 5 y. Conclusion: The chemo-immunotherapy combination is favorable compared to chemotherapy alone for the treatment of MCL. R-CHOP induction followed by rituximab maintenance in MCL shows favorable long-term safety and efficacy profile. Bortezomib substituting for vincristine in R-CHOP improves the efficacy outcomes. Ibrutinib-based regimens are superior to temsirolimus-based regimens. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

scholarly journals Clinical Characteristics, Treatment and Outcome of Patients with Mantle Cell Lymphoma: A Large, Multicenter Retrospective Analysis in China

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4522-4522
Author(s):  
Ping Yang ◽  
Shuozi Liu ◽  
Jing Wang ◽  
Wei Zhang ◽  
Hui Liu ◽  
...  
Keyword(s):  
High Risk ◽  
Mantle Cell Lymphoma ◽  
Maintenance Treatment ◽  
Cell Lymphoma ◽  
Risk Group ◽  
High Risk Group ◽  
High Dose ◽  
Mantle Cell ◽  
High Dose Cytarabine

Abstract Background Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non-Hodgkin lymphoma, most MCL cases have a rapid evolution and an aggressive behavior with an unfavorable outcome. Clinical features in mantle cell lymphoma appeared regional characteristics and the epidemiology of MCL in Asia is not accurate documented. MCL treatment opinions are not uniform between country/region within Asia and China. At present, the large-scale Asian patient-specific data for the treatment of MCL are lacking. Aims To obtain 'real world' clinical characteristics,treatment patterns and prognosis factors of MCL patients in China and to address the knowledge gap in Chinese MCL patients. Methods Patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. The median follow-up times was 36.0 months. The data of total 805 patients with mantle cell lymphoma were collected, 112 patients with incomplete clinical data, no chemotherapy and missing follow-up data were excluded. Finally, 693 patients with complete clinical data, treatment information and survival follow-up data were included in this study.Fully detailed information of patients, disease characteristics, treatments and outcomes were collected. Fisher's exact test or Pearson's Chi-squared test were used to compare categorical variables.Survival analysis was performed by Kaplan-Meier. Results The median age of the cohort was 60.0 years with a male-to-female ratio of 3.36:1. 477 patients (68.8%) were younger than 65 years at diagnosis.Advanced stage of diseases were 90.0%. Extranodal organ involvement was 83.4% and the most frequently involved extranodal organs were bone marrow(46.2%), spleen(36.1%), gastrointestinal tract(24.8) and oropharynx(17.7%). Blastic/pleomorphic mantle cell lymphoma accounted for 12.8%, and non-nodular mantle cell lymphoma accounted for 3.3%. Ki-67 more than 30% was 57.7% and Ki-67 ≥ 50% was 26.1%. The intermediate /high risk group was 49.8% according to MIPI score. The first-line therapeutic schedule is not completely unified, the most frequently regimen was CHOP/CHOP-like±R (n=312,45.0%) ,then high-dose cytarabine (n=222,32.0%), VR-CAP(n=44,6.3%), BR(n=30,4.3%), R-EPOCH (n = 17, 2.5%), FC / FCM±R regimen (n = 13,1.9%),and 55 patients(7.9%) uesd chemo-free regimen including IR / R2 / IR2 .Only 80 patients (11.5%) received autologous hematopoietic stem cell transplantation as consolidation therapy after chemotherapy remission. The ORR rate was 85.0%with 46.6% CR and 38.4% PR in the initial treatment.During the follow-up to June 2021(2-204months), 222 patients(32.0%) had died. The 5-year PFS and OS was 30.9% and 65.0%respectively.In the multivariate Cox regression model, ki67 ≥ 50% (HR 1.27, 95%CI 1.01-1.60, p = 0.038) ,stageⅢ/Ⅳ (HR1.56, 95%CI 1.05-2.33, p = 0.029),high- intermediate/high risk group accouding to MIPI-c (HR1.56, 95%CI 1.05-2.33, p = 0.008),spleen involvment (HR1.35, 95%CI 1.08-1.69, p = 0.009),without maintenance treatment (HR0.71, 95%CI 0.56-0.88, p = 0.003) ,SD/PD in inital treatment (HR6.20, 95%CI4.71-8.14, p &lt; 0.001) were independently associated with poorer PFS while ki67 ≥50% (HR 1.74, 95%CI 1.31-2.31, p&lt; 0.001),B symtom (HR 1.52, 95%CI 1.15-2.00, p = 0.003), high-intermediate/high risk group accouding to MIPI-c (HR1.43, 95%CI 1.24-1.64, p &lt; 0.001),without high-dose cytarabine (HR0.47, 95%CI 0.31-0.70 ,p &lt; 0.001) ,without maintenance treatment (HR0.40, 95%CI 0.28-0.58,p &lt; 0.001)and relapse/refractory state (HR 4.04, 95%CI 2.21-7.39, p &lt; 0.001) were independently associated with poorer OS. Conclusions This study describes the characteristics of mantle cell lymphoma in Chinese population with younger onset age and a higher tumor proliferation index. High dose cytarabine treatment and maintenance treatment have shown survival benefits in real-world.Recurrence and refractory is an important factor affecting survival,the strategy of combining molecular biological characteristics with novel strategies may improve outcome in these patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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