Dose-adjustment of lenalidomide according to patient age and vulnerability is feasible in relapsed or refractory multiple myeloma: retrospective analysis of 20 cases

Abstract Introduction Up-front autologous stem cell transplantation (ASCT-1) post front line therapy with novel agents is standard of care in newly diagnosed multiple myeloma. The role for salvage transplantation (ASCT-2) in relapsed patients after retreatment remains unclear in the era of the novel agents. Majority of published studies include patients treated in pre-thalidomide era. Our retrospective study investigates the safety and efficacy of ASCT-2 in patients exclusively treated with novel drugs both at upfront and at relapse. Primary end point was non relapse mortality (NRM) at day 100. Secondary end points were progression free survival from ASCT-2 (PFS-2) and overall survival (OS) Patients and Methods Thirty-nine patients (21 female and 18 male) underwent ASCT-2 at 4 centres between 2008 and 2013. At initial presentation all received thalidomide based treatments pre ASCT-1. Therapy at progression was bortezomib based in 92% and thalidomide in 8%. Melphalan 200 mg/m2 was used as conditioning for 90% of patients, 140 mg/m2 in 10%. OS and PFS-2 were calculated from ASCT-2. Statistical analysis was carried out using IBM SPSS 19 for Windows. Results Median progression free survival (PFS-1) post ASCT-1 was 35 (10-90) months with 4 patients receiving thalidomide maintenance. Median age at ASCT-2 was 60 (37-68) years with a median stem cell dose of 2.7×106 (2-7) CD34 cells /kg body weight. All patients engrafted with median times to neutrophil (>0.5) and platelet (>20) engraftment of 12 days each with a day+100 and 1 year NRM of 0%. With a median follow up from ASCT-2 of 18 (3-52) months, the median PFS-2 was 18 (12-24) months and OS was 42 (33-50) months. PFS-1 of greater than 18 months was associated with prolonged PFS-2 (19 vs. 6 months, p=0.001, log rank), however there was no statistical difference observed for PFS-1 beyond 24 months. Similarly PFS-1 >18 months predicted for improved OS (39 vs. 14 months, p=0.007, log rank). Age at ASCT-2(>or <60yrs) had no impact on PFS-2 or OS. Patient age>60 and with PFS-1 of >24 months had a median PFS-2 of 25months as compared to 14 months in patient age <60 with a PFS-1 of >24 months. Conclusion In the era of novel agents ASCT-2 can be safely delivered with 0% 1 year NRM. PFS-1 greater than 18 months gives better PFS-2 and OS suggesting a definite role of this therapy in a selected population Age greater than 60 years does not have adverse impact on either PFS or OS. Thus ASCT-2 should be considered in treatment strategies at disease progression and warrants further prospective studies Disclosures: No relevant conflicts of interest to declare.

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Real-World Outcomes With Generic Pomalidomide in Relapsed Refractory Multiple Myeloma—Experience From a Tertiary Care Cancer Center

JCO Global Oncology ◽

10.1200/go.20.00228 ◽

2021 ◽

pp. 361-367

Author(s):

Suresh Kumar Bondili ◽

Bhausaheb Bagal ◽

Abhinav Zawar ◽

Pradeep Ventrapati ◽

Jayashree Thorat ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Retrospective Analysis ◽

Tertiary Care ◽

Progression Free Survival ◽

Response Rates ◽

Cancer Center ◽

Free Survival ◽

Refractory Multiple Myeloma ◽

Median Progression Free Survival

PURPOSE The prognosis of relapsed and refractory multiple myeloma (RRMM) that is refractory to bortezomib and lenalidomide is very poor wherein the median survival is between 3 and 9 months. We did this retrospective analysis to study the pattern of utilization, tolerance, and outcomes with pomalidomide in these patients having RRMM. MATERIALS AND METHODS Retrospective analysis of all the patients who were treated with generic pomalidomide at Tata Memorial Centre, Mumbai, during the period of May 2017 to March 2019 was done. Patients with secretory disease and who had completed at least one cycle of pomalidomide were analyzed for response rates, toxicity, and survival outcomes. RESULTS A total of 81 patients received pomalidomide-based therapy during this study period, out of which 75 were included in the survival analysis. Forty-eight patients (59.3%) were refractory to both lenalidomide and bortezomib. Overall response rate was 58.7%. Five patients (6.7%) achieved complete response, very good partial response was seen in 13 patients (17.3%), and partial response was seen in 26 patients (34.7%). After a median follow-up of 11 months (range 2-27 months), median progression-free survival was 9.1 months (95% CI, 5.4 to 12.9 months). Median progression-free survival for patients who were refractory to both lenalidomide and bortezomib versus nonrefractory was 5.5 and 12.6 months, respectively, which was significant statistically ( P = .04, hazard ratio, 0.35, 95% CI, 0.28 to 0.97). The median overall survival was not reached. Important toxicities included anemia (28%), neutropenia (16%), pneumonia (16%), and venous thrombosis (5%). CONCLUSION Generic pomalidomide-based therapy is an effective option and is well tolerated in patients with RRMM. Higher response rates and longer survival seen in our study are possibly because of heterogeneity of the study population.

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Stem Cell Mobilization Following Initial Therapy with Lenalidomide and Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽

10.1182/blood.v112.11.3467.3467 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3467-3467 ◽

Cited By ~ 2

Author(s):

Shaji Kumar ◽

Martha Lacy ◽

Angela Dispenzieri ◽

Suzzanne Hayman ◽

Francis Buadi ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Initial Therapy ◽

Stem Cell Mobilization ◽

Patient Age ◽

Patient Âgé ◽

Cell Mobilization

Abstract Background: Autologous stem cell transplantation is an effective therapy for patients with multiple myeloma. We and others have previously reported the influence of lenalidomide based regimens on the ability to harvest adequate number of stem cells for successful transplantation. In order to identify factors predicting for poor mobilization we studied a large group of patients who underwent an attempt at stem cell mobilization after receiving lenalidomide and dexamethasone as primary therapy for myeloma. Methods: We identified sequential patients who received lenalidomide and dexamethasone as initial therapy for their myeloma and then underwent stem cell mobilization for immediate or future stem cell transplantation. Patients who received any other regimen prior to the stem cell mobilization were excluded. Between July 2004 and May 2008, 106 patients, satisfying the above criteria were identified from the Mayo Clinic transplant database. Medical records and collection sheets were examined for the data. Results: The median (range) age at mobilization was 60 yrs (29–75); 34 (32%) were over 65 yrs and 59 (55%) were males. The median duration of lenalidomide therapy was 4 months (range; 1–13). The strategy for stem cell mobilization was GCSF alone in 92 patients (87%), cyclophosphamide (CTX) and GCSF in 11 pts and 3 pts received AMD3100 and GCSF. Among the GCSF mobilized patients, 10 pts (11%) failed to collect at least 2.5 million cells required for one transplant, including 8 patients who never achieved the minimum peripheral count threshold to initiate the collection. Two of the 11 pts undergoing primary mobilization with CTX/GCSF failed to collect any cells, while all of the 3 pts mobilized with AMD3100 were successful. Five of these pts subsequently underwent successful salvage mobilization with CTX/GCSF, 1 with AMD3100, one failed to mobilize with CTX and the rest did not repeat mobilization. Given that the total CD34 collection and the number of days of collection are influenced by the CD34 goal, we examined patient characteristics that correlated with the CD34 collections over the first 2 days. Increasing patient age and the duration of lenalidomide therapy, both correlated with decreasing 2-day CD34 collection, while the time between last dose of lenalidomide and the start of GCSF had no effect. We then performed ROC analysis to find best cut-off points that predicted the inability to collect adequate (2.5 million) CD34 cells in 3 days. Lenalidomide therapy of more than 4 months (P =0.03) and age > 63 yrs (P = 0.04) best predicted inability to achieve this endpoint. In addition, a peripheral blood CD34 count < 5/uL on day 5 after start of GCSF was highly predictive of failure to reach this endpoint. Conclusions: Inability to collect adequate stem cells with lenalidomide appears to be related to patient age and the duration of lenalidomide therapy. We recommend early stem cell collection and storage, if a delayed transplantation approach is taken. Patients receiving more than 4 cycles of therapy and those over 65 years should undergo mobilization with CTX+G-CSF, rather than G-CSF alone. Majority of the patients who fail G-CSF based collection can be mobilized using CTX and G-CSF. Early identification of failures after G-CSF administration using the peripheral CD34 counts can potentially allow salvage using strategies such as AMD3100.

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