scholarly journals The Intensity of the Induction Regimen Does Not Affect Post-Transplant Survival Among Patients with Newly Diagnosed Mantle Cell Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2915-2915
Author(s):  
Melhem Solh ◽  
Asad Bashey ◽  
Lawrence E Morris ◽  
H. Kent Holland ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Research Funding ◽  
Cell Lymphoma ◽  
High Dose ◽  
Post Transplant ◽  
Mantle Cell ◽  
Induction Regimen ◽  
High Dose Cytarabine

Abstract The routine use of autologous stem cell transplantation (ASCT) in first remission have significantly improved outcomes for patients with mantle cell lymphoma (MCL) (Hermann et al, jco 2009). The choice of the most appropriate induction regimen prior to transplant remains a controversial topic. Adding high dose cytarabine to RCHOP among young patients (<65 years) results in superior PFS, higher toxicity but no improvement in overall survival when compared to RCHOP alone (Hermine O et al, Lancet 2016). The use of bendamustine/Rituxan (BR) compared to RCHOP in 2 randomized studies showed lower toxicity, higher PFS but similar overall survival. In this study, we investigated the effect of induction regimen intensity and the use of high dose cytarabine on post autologous stem cell transplant outcomes among MCL patients treated at our center. 59 patients who received ASCT for MCL between 2010 and 2020 were included in this analysis. Data were retrieved from our database where it was entered prospectively. Median age at diagnosis was 60 (45,76) years, stage IV (85%), B symptoms (32%), MIPI score (low 17%, intermediate 47%, high 28%) and ECOG performance 0-1 (81%). Induction regimen included BR (n=14), RCHOP (n=11), R-Hyper CVAD (n=14), RBAC(n=2) and RCHOP/RDHAP (n=18). 85% of patients were in CR and 15% in PR at time of transplant. All patients underwent chemo mobilization with a median time from diagnosis to transplant of 251 (119,1372) days. 30 patients (51%) received post-transplant rituximab maintenance. Patients were compared into 2 groups based on the use of high dose cytarabine in their induction regimen (table 1). Patients who received high dose cytarabine were younger and had a shorter time from diagnosis to transplant that patients who were treated without cytarabine. Survival endpoints for cytarabine based and no cytarabine based induction at 5 years post-transplant were as follows OS (82% vs 69%), DFS (65% vs 50%), Non-relapse mortality (4% vs 9%) and relapse (31% vs 41%) respectively ( figure 1). A multivariable cox analysis for OS, DFS, NRM and relapse showed that cytarabine had no effect on any of the endpoints. For OS, B symptoms and worse ECOG performance at Diagnosis (>=2) were associated with worse OS. For relapse, higher MIPI score and no use of Rituxan maintenance resulted in higher relapse. In conclusion, our data shows that among MCL patients receiving ASCT, the use of more intensive cytarabine based induction does not clearly improve long-term outcomes It is possible that use of ASCT compensates for the use of a less intense induction regimen. Disease (MIPI), Patient (ECOG)characteristics and use of post-transplant maintenance are factors that contribute to post transplant outcomes. Figure 1 Figure 1. Disclosures Solh: Jazz Pharmaceuticals: Consultancy; Partner Therapeutics: Research Funding; BMS: Consultancy; ADCT Therapeutics: Consultancy, Research Funding.

scholarly journals Long-term outcomes of high dose treatment and autologous stem cell transplantation in follicular and mantle cell lymphomas – a single centre experience

2016 ◽  
Vol 51 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Lucka Boltezar ◽  
Karlo Pintaric ◽  
Jože Pretnar ◽  
Maja Pohar Perme ◽  
Barbara Jezersek Novakovic
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
High Dose ◽  
High Dose Treatment ◽  
Mantle Cell

Abstract Background Advanced follicular lymphoma (FL) and mantle cell lymphoma (MCL) are incurable diseases with conventional treatment. The high dose treatment (HDT) with autologous stem cell transplantation (ASCT), however, offers a certain proportion of these patients the prospect of a prolonged disease-free and overall survival. The aim of this study was to investigate the event free survival (EFS) and overall survival (OS) in patients with FL and MCL treated with ASCT. Patients and methods Seventeen patients with FL and 29 patients with MCL were included, 15 of them were transplanted to consolidate the response to second line treatment and 24 to consolidate their first remission, respectively. All were conditioned with total body irradiation (TBI) and high dose cyclophosphamide between 2006 and 2014 and all were transplanted with peripheral blood stem cells. Results The estimated 5-year OS for FL was 87.8% (95% confidence interval [CI] 59.5%–96.8%) and for MCL 79.3% (95% CI 56.1%–91.1%), respectively. The estimated 5-year EFS for FL was 76.0% (95% CI 48.0%–90.3%) and for MCL 69.8% (95% CI 45.5%–84.8%), respectively. There were no secondary hematological malignancies observed in either group. Conclusions Based on above results, the ASCT with TBI is a good treatment option in terms of long-term survival for patients with follicular and mantle cell lymphoma demonstrating a relatively low rate of late toxicities and secondary malignancies.

Consolidation with High Dose Therapy and Autologous Stem Cell Transplant Improves Survival for Patients with Mantle Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2006-2006
Author(s):  
Loretta Nastoupil ◽  
Pareen J Shenoy ◽  
Alex Ambinder ◽  
Miray Seward ◽  
Ajay K. Nooka ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
High Dose ◽  
High Dose Therapy ◽  
Mantle Cell ◽  
Induction Regimen ◽  
Baseline Characteristics ◽  
Ecog Ps

Abstract Abstract 2006 Background: Mantle cell lymphoma (MCL) comprises 5–7% of all non-Hodgkin lymphomaand remains incurable with conventional chemotherapeutic approaches. Some clinical series and trials suggest that outcomes are improved with intensive induction containing cytarabine (Ara-C) and/or the use of high dose therapy (HDT) and autologous stem-cell transplantation (ASCT) once patients (pts) achieve remission. What is not apparent are the contributions of each and which prognostic factors influence outcomes. We examined our single center experience with initial management strategies for pts diagnosed with MCL between 1995 and 2011 and compared outcomes of CHOP±R (rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone), an intensive induction regimen HCVAD±R (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate/cytarabine) in patients who subsequently underwent observation or HDT/ASCT. Methods: To examine the effectiveness of CHOP±R, HCVAD±R and HDT/ASCT, and the contributions of each to overall survival (OS), we conducted an IRB-approved retrospective review of consecutive cases of MCL identified from our database. Responsesfollowing the first management strategy were retrospectively assessed using International Working Group Criteria (JCO 1999). Descriptive statistics for the baseline characteristics of pts who received CHOP±R and HCVAD±R were compared using Chi-square tests. Kaplan–Meier estimation was used to evaluate OS and the treatment regimens were compared with the log-rank test. Toevaluate prognostic factors and the effects of treatment on OS, Cox proportional hazards models were used controlling for sex, race, stage, presence of B-symptoms, MIPI score, and those who underwent consolidation with HDT/ASCT. Results: 103 ptswere identified with a median age of 58 (range 32–79 years), 27% were ≥65 years of age, 80% were male, 77% were white, 96% had an ECOG PS ≤1, 93% were advanced stage (III/IV), and the majority had a low risk MIPI score (53%). 43% (N=44) received CHOP±R (mean # of cycles 5.3, median 6, range 1–8) and the remaining 57% received HCVAD±R (N=59, mean # of cycles 4.5, median 4, range 1–12). 65% of HCVAD pts and 27% of CHOP pts received R. No significant differenceswere observed in the baseline characteristics of the two groups: age (59 years CHOP±R vs. 57 HCVAD±R, p=0.06), presence of B symptoms (32% vs. 31%, p=0.77), stage (III/IV, 91% vs. 95%, p=0.69), or MIPI score (low 50% vs. 56%, p=0.97). Of the pts who were consolidated with a transplant (N=47), median age was 58, 85% were male, 32% had B-symptoms, all had an ECOG PS ≤1, 26% had an LDH>ULN, 51% had a low MIPI, and 81% received HCVAD±R as induction. In comparison to those observed, the only significant differences were ECOG PS (8% ≥2, p=0.05) and induction regimen (63% CHOP±R, p<0.001). There were no significant differences in 5-year OS for CHOP±R: 64% (95% CI 44–79%) and HCVAD±R:68% (52–80%). There was a significant difference in 5-year OS for patients who underwent HDT/ASCT vs. those who did not consolidate with transplant (74% vs. 59%, p=0.03). 5-year OS for those treated with HCVAD±R + HDT/ASCT was not significantly different from the rest of the pts74% vs. 61% (p=0.19). After controlling for clinical confounders including sex, race, stage, presence of B-symptoms, consolidation with HDT/ASCT was associated with superior OS (HR 0.46 95% CI 0.22–0.93) while having a high MIPI score was associated with inferior OS (HR 3.79, 95% 1.59–9.01). Conclusions: Our single institution experience for untreated MCL pts demonstrates favorable 5-year OS independent of induction chemotherapy. Patients who underwent consolidation with HDT/ASCT had superior OS compared to those who did not. Disclosures: Flowers: Genentech/Roche (unpaid): Consultancy; Millennium (unpaid): Consultancy; Celgene: Consultancy; Celgene: Research Funding; Spectrum: Research Funding; Millennium: Research Funding; Gilead: Research Funding; Janssen: Research Funding.

Modified VR-CAP, Alternating With Rituximab and High-dose Cytarabine: An Effective Pre-transplant Induction Regimen for Mantle Cell Lymphoma

2019 ◽  
Vol 19 (1) ◽  
pp. 48-52
Author(s):  
Stephen D. Smith ◽  
Shruti Gandhy ◽  
Ajay K. Gopal ◽  
Prathima Reddy ◽  
Mazyar Shadman ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
High Dose ◽  
Mantle Cell ◽  
Induction Regimen ◽  
High Dose Cytarabine

scholarly journals Mantle Cell Lymphoma International Prognostic Index but Not Pretransplantation Induction Regimen Predicts Survival for Patients With Mantle-Cell Lymphoma Receiving High-Dose Therapy and Autologous Stem-Cell Transplantation

2011 ◽  
Vol 29 (22) ◽  
pp. 3023-3029 ◽  
Author(s):  
Lihua E. Budde ◽  
Katherine A. Guthrie ◽  
Brian G. Till ◽  
Oliver W. Press ◽  
Thomas R. Chauncey ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
High Dose ◽  
High Dose Therapy ◽  
Induction Group ◽  
Mantle Cell ◽  
Induction Regimen

PurposeHigh-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) are frequently used in an attempt to improve outcome in patients with mantle-cell lymphoma (MCL); however, the importance of intensive induction regimens before transplantation is unknown.Patients and MethodsTo address this question, we evaluated baseline characteristics, time to treatment, induction regimen, disease status at the time of transplantation, and MIPI score at diagnosis and their associations with survival in 118 consecutive patients with MCL who received HDT and ASCT at our centers.ResultsThe MIPI was independently associated with survival after transplantation in all 118 patients (hazard ratio [HR], 3.5; P < .001) and in the 85 patients who underwent ASCT as initial consolidation (HR, 7.2; P < .001). Overall survival rates were 93%, 60%, and 32% at 2.5 years from ASCT for all patients with low-, intermediate-, and high-risk MIPI, respectively. Low-risk MIPI scores were more common in the intensive induction group than the standard induction group in all patients (64% v 46%, respectively; P = .03) and in the initial consolidation group (66% v 45%, respectively; P = .03). After adjustment for the MIPI, an intensive induction regimen was not associated with improved survival after transplantation in all patients (HR, 0.5; P = .10), the initial consolidation group (HR, 1.1; P = .86), or patients ≤ 60 years old (HR, 0.6; P = .50). Observation of more than 3 months before initiating therapy did not yield inferior survival (HR, 2.1; P = .12) after adjustment for the MIPI in patients receiving ASCT.ConclusionAn intensive induction regimen before HDT and ASCT was not associated with improved survival after adjusting for differences in MIPI scores at diagnosis.

Is There Still a Place for Total Body Irradiation (TBI) In the Conditioning Regimen of Autologous Stem Cell Transplantation In Mantle Cell Lymphoma ?: a Retrospective Study From the Lymphoma Working Party of the EBMT

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 688-688 ◽  
Author(s):  
Marie T Rubio ◽  
Ariane Boumendil ◽  
Jian Jian Luan ◽  
Carmen Canals ◽  
Francois Lefrère ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retrospective Study ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
Disease Status ◽  
High Dose ◽  
Mantle Cell ◽  
High Dose Cytarabine

Abstract Abstract 688 Prognosis of Mantle cell lymphoma (MCL) has recently improved by the use of combination of monoclonal anti-CD20 immunotherapy, high-dose cytarabine containing regimen and autologous stem cell transplantation (ASCT). During the last decade the use of TBI, as part of the conditioning regimen of ASCT, has drastically decreased. This attitude is questionable since first, MCL cell lines exhibit a high sensitivity to radiotherapy in vitro and second, a retrospective study including 18 patients suggested that TBI may improve the EFS after ASCT in MCL (Milpied et al, BMT 1998). Aim. We performed a large retrospective study from the EBMT registry to assess the role of TBI in the conditioning regimen of ASCT in MCL. Patients and methods. All patients who underwent an ASCT between 2000 and 2007 in complete or first partial remission (CR/PR1) registered within the EBMT data-base with complete MedB forms available were eligible for this study. Results. Altogether 418 patients met the eligibility criteria. Median age was 51 years (range 29 to 65 years). At diagnosis 93% of the patients presented with a stage III/IV disease. Most of the patients (85%) had received one line of chemotherapy prior to ASCT. According to reported treatments, 122 patients (31%) had received Rituximab (R) and high-dose cytarabine (HD-Cyt) before transplantation and 111 patients (29%) had not received any of these drugs. At transplant, 283 patients (68%) were in CR and 135 (32%) in PR1. Conditioning regimen for ASCT contained TBI in 152 patients (36.5%) and consisted on a BEAM-based chemotherapy in 92% of the 266 patients transplanted with a non-TBI regimen. Stem cell source was peripheral blood for 99.3% of patients. With a median follow-up of 29 months, median overall and disease free survival (OS and DFS) of all patients were 99 and 57 months, respectively. Disease status at transplant appeared as a significant predictive factor for DFS and relapse incidence (RI) but at the time of analysis had no impact on OS. In comparison to patients transplanted in CR, those transplanted in PR1 had an impaired DFS (median DFS 52 months versus 40 months, respectively) (RR= 1,53, 95% CI 1.10–2.14, p=0.01) with an increased incidence of relapse (RR= 1.49, 95% CI 1.04–2.13, p= 0.03). Since we found a significant interaction between the use of TBI and disease status on the incidence of relapse, all further analysis were stratified on disease status at transplant. The use of R and HD-Cyt before ASCT or TBI in the conditioning of ASCT did not have any impact on OS, DFS and RI of patients transplanted in CR. In contrast, for patients transplanted in PR1, pre-transplant treatment with R and HD-Cyt was associated with a prolonged DFS in comparison to those who did not receive these treatments (median DFS 52 months versus 27 months, respectively, p=0.0891). Moreover, in patients in PR1 at transplant, the use of TBI was associated with a significant reduction of the incidence of relapse in both univariate and multivariate analysis (p=0.034 and RR= 0.409, 95% CI 0.213–0.786, p=0.007, respectively). There was a trend to a better DFS in patients transplanted in PR1 with TBI (median DFS 60 months with TBI versus 33 months without TBI, p=0.123). At the time of analysis, overall survival and non relapse mortality (NRM) were similar between patients who received TBI and those who did not. Three secondary malignancies were reported in this series of patients with two occurring in the TBI group Conclusion. In this retrospective series of autografted MCL, the risk of relapse after ASCT is mainly dependant on the disease status at transplant. TBI or other radiotherapy-based conditioning can be probably avoided in patients transplanted in CR but should still be considered in patients who can not achieve a better response than PR at transplant. Disclosures: No relevant conflicts of interest to declare.

Rituximab Maintenance after Autologous Stem Cell Transplantation Prolongs Survival in Younger Patients with Mantle Cell Lymphoma: Final Results of the Randomized Phase 3 LyMa Trial of the Lysa/Goelams Group

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 145-145 ◽  
Author(s):  
Steven Le Gouill ◽  
Catherine Thieblemont ◽  
Lucie Oberic ◽  
Anne Moreau ◽  
Krimo Bouabdallah ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Standard Of Care ◽  
High Dose ◽  
Advisory Committees ◽  
Free Survival ◽  
Mantle Cell ◽  
High Dose Cytarabine

Abstract Mantle cell lymphoma (MCL) accounts for approximately 6% of non-Hodgkin's Lymphoma (NHL) in adults. MCL commonly responds to initial therapy but inevitably patients relapse and response duration decreases from one salvage therapy to the next. Indeed, there is an urgent need to control and/or eradicate residual MCL cells that are responsible for early and late relapses. Maintenance with Rituximab (RM) after R-CHOP has been shown to prolong OS in elderly MCL patients treated with R-CHOP (Kluin-Nelemans et al. NEJM). Induction with high-dose cytarabine followed by autologous stem cell transplant (ASCT) consolidation is standard of care for young patients but RM after ASCT has never been investigated so far. The LyMa trial (ClinicalTrials.gov, NCT00921414) is a prospective international randomized phase III trial that investigated RM after ASCT in young previously untreated MCL patients. Patients were included at diagnosis (<66y; stage >I, untreated, diagnosis of MCL according to WHO 2008 classification). Induction immuno-chemotherapy consisted of 4 courses of R-DHAP every 21 days (Rituximab, Dexamethasone, High-dose cytarabine, salt Platinum) followed by ASCT consolidation. Patients who were not in response (CR/CRu or PR) after R-DHAP received 4 additional courses of R-CHOP-14 before ASCT. The conditioning regimen for ASCT was R-BEAM. Patients in response after ASCT were randomized (1:1) between RM or no RM. RM consisted of one infusion of Rituximab (375mg/m2) every 2 months for 3 years. The primary endpoint was event-free survival (EFS) calculated from time of randomization; events were defined as disease progression, relapse, death, severe infection or allergy to Rituximab. Progression-free survival (PFS) and overall survival (OS) from time of diagnosis and time of randomization were secondary endpoints. The interim analysis showed a trend for a longer EFS and PFS in favor of RM arm. (Le Gouill et al, ASH 2014, abs 146). Herein, we present the results of the final analysis. RESULTS. Two hundred and ninety nine patients were enrolled from September 2008 to August 2012. Demographic and clinical characteristics of the patients were as followed: median age of 57y (27-65), 79% of male, MIPI-low in 53.2%, MIPI-I in 27.4% and MIPI-H in 19.4%. After inclusion, 277 patients completed the 4 courses of R-DHAP. The CR/CRu rate after R-DHAP was 77.3% and ORR was 89.3%. Twenty patients received R-CHOP. In all, 257 patients (including 12 patients who received R-DHAP/R-CHOP) underwent ASCT. After ASCT, 240 patients were randomized (RM, n=120; no RM, n=120). Median follow-up (mFU) from inclusion and from randomization were 54.4m (52.7-59.2) and 50.2m (46.5-54.2), respectively. The mPFS and mOS from inclusion in an intention to treat analysis were not reached; the 4y-PFS and OS were 67.8% (95%CI, 62.1 to 72.8) and 78% (95%CI; 72.8 to 82.3), respectively. According to EFS definition, 47 (39.2%) patients had an event in the no RM versus 25 (20.8%) in the RM arm. The mEFS from randomization was not reached in both arms. The 4y-EFS was 61.4% (95%CI; 51.3 to 69.9) in the no RM arm vs 78.9% (95%CI; 69.6 to 85.6) in the RM arm (p=0.0012). The EFS duration was significantly superior in the RM arm with a 54.3% reduction in the risk of event (Hazard ratio (HR)= 0.457; 95%CI, 0.28 to 0.74; p=0.0016). The median PFS and OS from randomization were not reached in both arms. The 4y-PFS and OS from randomization were superior in the RM arm: 82.2% (95%CI; 73.2 to 88.4) vs 64.6% (95%CI; 54.6 to 73) (p=0.0005) and 88.7% (95%CI; 80.7 to 93.5) vs 81.4% (95%CI; 72.3 to 87.7)(p=0.0413). Patients in the RM arm had a 60% reduction of risk of progression (HR=0.4; 95%CI, 0.23 to 0.68; p=0.0007) and a 50% reduction of risk of death (HR=0.5; 95%CI, 0.25 to 0.98; p=0.0454). The per protocol analysis yielded similar results. In conclusion, The LyMa trial demonstrates for the first time that RM after ASCT prolongs EFS, PFS and OS. Thus, 4 courses of R-DHAP plus ASCT (without TBI) followed by RM maintenance (one infusion every 2 month for 3 years) is a new standard of care for young MCL patients. Disclosures Thieblemont: Gilead: Consultancy; Roche: Consultancy; Janssen: Consultancy. Ribrag:Pharmamar: Membership on an entity's Board of Directors or advisory committees; Esai: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; NanoString: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; ArgenX: Research Funding. Casasnovas:BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; ROCHE: Consultancy, Honoraria, Research Funding. Haioun:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hermine:Celgene: Research Funding; AB science: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Novartis: Research Funding; Alexion: Research Funding.

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