Rituximab (R) + Hypercvad Alternating with R-Methotrexate/Cytarabine after 9 Years: Continued High Rate of Failure-Free Survival in Untreated Mantle Cell Lymphoma (MCL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 833-833 ◽  
Author(s):  
Jorge Romaguera ◽  
Luis Fayad ◽  
Alma Rodriguez ◽  
Fb Hagemeister ◽  
Barbara Pro ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Response ◽  
Serum Lactate ◽  
High Rate ◽  
Serum Lactate Dehydrogenase ◽  
High Dose ◽  
Free Survival ◽  
Mantle Cell ◽  
Rate Of Failure

Abstract MCL has a poor outcome with current non-intense therapies. We present an update of our results utilizing an intense chemotherapy regimen comprising fractionated cyclophosphamide, doxorubicin, vincristine and dexamethasone to which rituximab has been added (R-HyperCVAD, one cycle), alternating with rituximab and high dose methotrexate/cytarabine (R-MA, one cycle) for a total of 6–8 cycles (J Clin Oncol 2006 Feb 1;24(4):724). Treatment was started at most within 2 months from the initial evaluation. Overall survival (OS) was defined as the time from start of treatment until recurrence or death from any cause. Failure-free survival (FFS) was defined as the time from start of treatment until recurrence or death from toxicity or death from treatment-related malignancy. Of 97 consecutive evaluable patients, 87% achieved a complete response (CR) or unconfirmed CR after 6 cycles and did not receive additional therapy. With a median follow up on 84 months (7 years), the overall survival and failure-free survival at 7 years was 60% and 43%, respectively. Among patients 65 years of age or younger, the 7-year OS and FFS was 68% and 52%, respectively. Important prognostic variables included age (65 yrs or less vs > 65 yrs; initial serum B2 microglobulin 3 or less mg/dL vs > 3); and initial serum lactate dehydrogenase (normal vs > normal). Further subset analysis will be presented at the meeting. Figure Figure

scholarly journals Primary Clinical Response of Relmacabtagene Autoleucel in Adults with Relapsed/Refractory Follicular Lymphoma (r/r FL) in China

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2434-2434
Author(s):  
Yuqin Song ◽  
Zhitao Ying ◽  
Haiyan Yang ◽  
Ye Guo ◽  
Wenyu Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Duration ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
Free Survival ◽  
Duration Of Response

Abstract Background Most patients (pts) with r/r FL remain incurable and eventually relapse or progress. Previously, a Ph1 study of relma-cel (NCT03344367) had demonstrated preliminary safety and efficacy in r/r B-NHL pts, including those with r/r FL. A Ph2 pivotal study in r/r FL pts had been enrolled and preliminary efficacy, safety and PK was presented. Methods Adult pts were eligible with histologically confirmed grade (Gr)1-3a r/r FL on the basis of the 2016 WHO Classification, having failed ≥ 2-line prior therapies or relapsed after auto-HSCT, without allogeneic transplant within 90 days or primary central nervous system (CNS) lymphoma, and with ECOG performance score of 0-1. Pts were randomized to receive either 100×10 6 (low dose) or 150×10 6 (high dose) relma-cel (1:1) following fludarabine 25 mg/m 2 & cyclophosphamide 250 mg/m 2 daily×3. Pts were evaluated for efficacy (Cheson, 2014), toxicity (cytokine release syndrome [CRS] by Lee 2014, and others by CTCAE v4.03), and PK (by qPCR and flow cytometry). Primary endpoint was complete response rate (CRR). Secondary endpoints included objective response rate (ORR), frequency/severity of AEs, duration of response (DOR), duration of complete response (DoCR), duration of partial response (DoPR), time to primary remission (TTR), time to primary complete remission (TTCR), progression free survival (PFS), overall survival (OS), and CAR-T cell expansion. Disease response was by investigator assessment, a sensitivity analysis was also conducted using an independent review committee. Results Between June 2018 and June 2021, 28 r/r FL pts were enrolled and treated. As of the data cut-off of June 11, 2021, 20 pts were treated with relma-cel with ≥ 1 month of follow-up. Among these 20 pts, the median age was 54.5 years (range, 36-71), 50% of pts were male, 85% had ECOG 0, 10% had a sum of perpendicular diameters (SPD) ≥ 5000 mm 2, and 36% (5/14) had a FLIPI2 score≥ 3. Pts had received a median of 3.5 prior lines of therapy, 6 (30%) pts had received at least five lines of treatment and 65% were refractory to last prior treatment, 85% were relapsed, 50% were both relapsed and refractory. Relma-cel was successfully manufactured in all pts. Best ORR was 100% (19/19), and best CRR was 95% (18/19). For the mITT (n=19, one pt who developed gastric adenocarcinoma, was excluded, but also achieved CR), ORR at 1 month was 100%(19/19) and CRR was 63% (12/19). CRR at 3 months for 17 pts > 3 months post treatment, was 82%(14/17). At a median follow-up of 8.9 months, the median duration of response [DOR], progression-free survival (PFS) and overall survival (OS) were not reached. Twenty pts who received relma-cel were evaluable for safety. Gr ≥3 AEs related to relma-cel occurred in 80% of pts, most commonly neutrophil count decreased (35%), lymphocyte count decreased (30%) and white blood cell count decreased (25%). CRS occurred in 35% (all Gr 1), and only 2 pts received tocilizumab. Median CRS onset was 7 days (range, 5-9), with median duration of 5 days. Two (10%) pts experience neurotoxicity (NT), both Gr 1, with onsets of 4 and 9 days, and duration of 25 and 7 days, respectively. No deaths occurred. Safety data, tocilizumab/steroids usage and PK parameters are shown in the Table. Conclusion With median follow-up of 8.9 months, relma-cel treatment in r/r FL pts had resulted in high tumor remission rates and a manageable toxicity profile in the first 20 pts treated. Data for additional patients will be presented. Table： The summary of AEs (AE, TEAE, CRS, NT), the usage of tocilizumab/steroids and PK Parameters Figure 1 Figure 1. Disclosures Yang: JW Therapeutics: Current Employment. Zhang: JW Therapeutics: Current Employment. Ma: JW Therapeutics: Current Employment. Zhou: JW Therapeutics: Current Employment. Zheng: JW Therapeutics: Current Employment.

Continuous Immuno-Chemotherapy Followed by High Dose and Autologous Cell Transplantation May Improve the Event-Free-Survival in Mantle Cell Lymphoma Patients. Experience at the European Institute of Oncology in Milan.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5116-5116
Author(s):  
Simona Bassi ◽  
Alessandra Alietti ◽  
Chiara Corsini ◽  
Federica Gigli ◽  
Paola Bertazzoni ◽  
...  
Keyword(s):  
Median Time ◽  
Standard Dose ◽  
Complete Response ◽  
High Dose ◽  
Free Survival ◽  
Autologous Cell ◽  
Mantle Cell ◽  
High Dose Cytarabine ◽  
Autologous Cell Transplantation

Abstract Mantle cell lymphoma (MCL) is an aggressive disease, currently incurable with standard-dose chemotherapy. Autologous cell transplantation (ASCT) is frequently considered a therapeutical approach in MCL, despite not generally being curative. In controlled studies upfront ASCT showed a significant event-free survival advantage, that might be improved by the addition of the anti-CD20 monoclonal-antibody (MoAb) (Rituximab®) in the myeloablative regimen. Based on these evidences, we prospectively analysed our patients (pts) affected by MCL, who received a continuous Rituximab administration in course on treatment. From May 2000 to the present we treated 22 pts with histological diagnosis of MCL, including 16 pts (73%) newly diagnosed. The majority were male (15/22) and the median age at diagnosis was 56 years old (range 35–66). Disease was stage III–IV: 21 pts with bone marrow involvement in 60%. Eleven pts presented extranodal involvement. The induction schedule included 2–4 CHOP-like regimen with MoAb (R-ACOD), followed by mobilization chemotherapy with cyclophosphamide, MoAb and G-CSF. Harvest was performed successfully in all pts with a median number of CD34-positive cells of 8.0 x 106/Kg (1.9–22.8 106/Kg). Subsequently the pts received 2 cycles of high-dose, cytarabine-based regimen with MoAb (R-ESHAP). Rituximab injections were given at standard dose (375 mg/mq). Before ASCT, 11 pts (50%) were in complete response (CR); in particularly 5 of them who were pretreated. Eight achieved partial response, while one was in progression. Two pts were not restaged. One patient did not undergo ASCT, because of serious pulmonary infection after high-dose cytarabine. In terms of conditioning regimen all pts received Rituximab (375 mg/mq), Melphalan (180mg/mq) in association with either Idarubicin (15mg/mq for 3 days) in 13 pts and or Novantrone (60 mg/mq for 1 day) in 8 pts. After stem cell reinfusion and G-CSF from Day +5, the median time to recovery (neutrophil counts >0.5x103) was 14 days (range 13–28 days) in the first regimen versus 10 days (range 8–11 days) in the more recent regimen. During aplasia the infection rate was low, as a matter of fact we observed just two episodes of pneumonia, that resolved at neutrophil recovery. No toxic death was reported. Response at 3 months after ASCT was evaluable in 19 patients (90%); one was lost at follow-up, while one has been transplanted one month ago. Seventy patients (80%) achieved complete response, maintained in 11 of them after a median time of 23 month (range 10–79) after ASCT; seven of them were in complete response before the transplant procedure. With a median time of 27 months (range 9–46 months) 7 patients progressed and 4 of these died because of lymphoma. Our study supports that ASCT can be considered a valid approach to induce high response rate. To enhance the ASCT outcomes, the addition of Rituximab can be considered a feasible approach associated with its “purging in vivo” effect. Long-term disease control might be reflected upon a plateau in the survival curve, but a randomised study and longer follow up is warranted.

Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity.

1988 ◽  
Vol 6 (9) ◽  
pp. 1491-1500 ◽  
Author(s):  
A E Chang ◽  
T Kinsella ◽  
E Glatstein ◽  
A R Baker ◽  
W F Sindelar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Dose Regimen ◽  
Soft Tissue Sarcomas ◽  
Disease Free Survival ◽  
High Dose ◽  
Free Survival ◽  
High Dose Regimen ◽  
Disease Free

We have previously reported the results of a randomized trial that demonstrated the survival benefit of adjuvant chemotherapy in the treatment of patients with high-grade extremity sarcomas compared with no chemotherapy. This regimen included doxorubicin, cyclophosphamide, and methotrexate. This report updates and extends our experience. The median follow-up of this trial is now 7.1 years and reveals a 5-year disease-free survival of 75% and 54% for chemotherapy and no chemotherapy groups, respectively (two-sided P [P2] = .037). The 5-year overall survival for patients in this trial was 83% and 60% for the chemotherapy and no chemotherapy groups, respectively, with a trend towards improved survival in the chemotherapy arm (P2 = .124). Because of doxorubicin-induced cardiomyopathy we performed a subsequent randomized trial comparing this high-dose regimen to reduced cumulative doses of doxorubicin and cyclophosphamide without methotrexate. Eighty-eight patients were entered into this trial which has a median follow-up of 4.4 years. The 5-year disease-free and overall survival for patients treated with the reduced doses of chemotherapy was 72% and 75%, respectively, and was not significantly different from the high-dose regimen. No patients developed congestive heart failure on this study. We conclude that adjuvant chemotherapy improves disease-free survival in patients with extremity soft-tissue sarcomas. The overall survival advantage in patients receiving adjuvant chemotherapy in our initial randomized high-dose chemotherapy trial has diminished though it continues to favor the chemotherapy group. A reduced-dose chemotherapy regimen was found to be comparable to the high-dose regimen.

Treatment of Indolent B-Cell Nonfollicular Lymphomas: Final Results of the LL01 Randomized Trial of the Gruppo Italiano per lo Studio dei Linfomi

2003 ◽  
Vol 21 (8) ◽  
pp. 1459-1465 ◽  
Author(s):  
Luca Baldini ◽  
Maura Brugiatelli ◽  
Stefano Luminari ◽  
Marco Lombardo ◽  
Francesco Merli ◽  
...  
Keyword(s):  
B Cell ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
High Dose ◽  
Free Survival ◽  
Significant Difference

Purpose: To evaluate the effect of epirubicin on therapeutic response and survival in patients with indolent nonfollicular B-cell lymphomas (INFL) treated with pulsed high-dose chlorambucil. Patients and Methods: A total of 170 untreated patients with advanced/active INFL were randomly assigned to receive either eight cycles of high-dose chlorambucil (15 mg/m2/d) plus prednisone (100 mg/d) for 5 days (HD-CHL-P; arm A) or eight cycles of HD-CHL-P plus epirubicin 60 mg/m2 intravenous on day 1 (arm B). The responding patients were randomly assigned to either maintenance therapy with interferon alfa (IFNα-2a; 3 MU, three times weekly) for 12 months or observation. Results: There were 160 assessable patients (82 males, 78 females; median age, 63 years; range, 33 to 77 years); 77 patients were assigned to arm A, and 83 were assigned to arm B. Induction therapy led to 47 complete responses (CRs; 29.4%) and 68 partial responses (PRs; 42.5%), with no significant difference between the two arms (60 CR + PR in arm A [77.9%] and 55 CR + PR in arm B [66.3%]; P = .07). After a median follow-up of 38 months (range, 2 to 103 months), there was no between-group difference in overall survival (OS; P = .45), failure-free survival (P = .07), or progression-free survival (PFS; P = .5). Eighty-eight patients were randomly assigned to either IFNα-2a (n = 43) or observation (n = 45), without any difference in 3-year PFS (44% and 42%, respectively). Univariate analysis showed that OS was influenced by age, anemia, serum lactate dehydrogenase levels, and International Prognostic Index distribution; multivariate analysis identified age and anemia as having influence on OS. Conclusion: HD-CHL-P treatment outcome in INFL patients was good (50% 3-year PFS, minimal toxicity, and low costs); epirubicin did not add any advantage. One-year IFNα maintenance treatment did not prolong response duration.

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.

Randomized trial of high-dose chemotherapy with autologous haematopoietic stem cell support vs. standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: Overall survival after 6 years of follow up

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 672-672 ◽  
Author(s):  
A. R. Zander ◽  
N. Kroeger ◽  
C. Schmoor ◽  
W. Krueger ◽  
V. Moebus ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Standard Dose ◽  
Interactive Effect ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Grade Iii

672 Background: Investigation of high dose chemotherapy (HD-CT) supported by autologous hematopoietic stem cell transplantation compared with standard dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more axillary lymph nodes. Methods: Between November 1993 and September 2000 307 patients were randomized to receive the following cycles of Epirubicin (90 mg/m2), Cyclophosphamide (600 mg/m2) intervenously (every 21 days) either HD-CT of Cyclophosphamide (1500 mg/m2), Thiotepa (150 mg/m2) and Mitoxantrone (10 mg/m2) intervenously for 4 consecutive days followed by stem cell transplantation or standard dose chemotherapy SDCT in 3 cycles of Cyclophosphamide (500 mg/m2), Methotrexate (40 mg/m2) and Fluoruracil (600 mg/m2) intervenously on days 1 and 8 every 28 days. The primary end points were event-free survival and overall survival. Results: After a median follow-up of 6.1 years 166 events with respect to event-free survival (SD-CT: 91, HD-CT: 75) and 123 with respect to overall survival (SD-CT: 66 and HD-CT: 57) have been observed. The hazard ratio of HD-CT versus SD-CT is estimated as 0,80, p = 0,15. The hazard ratio for overall survival for high dose chemotherapy versus standard dose chemotherapy is estimated as 0,84, p = 0,33. Analysing the effect of treatment on event-free survival premenopausal patients, patients with tumor grade III and ER-positive patients had a better outcome with HD-CT with an interactive effect of 2.5 and 1.4. The significance was only shown in grade III patients in favour of HD-CT, (p = 0,049). The interactive effect of HD-CT with prognostic factors did not reach significance for overall survival. Conclusion: Even with a follow-up of 6.1 years there was only a trend in favour of high dose chemotherapy with respect to overall survival but without a statistical significance. A proper meta-analysis needs to be undertaken for an evaluation of subgroups of patients which might benefit from this treatment approach. No significant financial relationships to disclose.

Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: Updated Follow-Up and Improved Survival

2014 ◽  
Vol 32 (7) ◽  
pp. 634-640 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Alessandra Larocca ◽  
Davide Rossi ◽  
Francesco Di Raimondo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Response Rate ◽  
Complete Response Rate ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Grade 3 ◽  
To Receive

Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients. Conclusion Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.

Sign in / Sign up

Export Citation Format

Share Document