Bortezomib and melphalan conditioning increases the rate of complete response and MRD negativity for patients with multiple myeloma undergoing single autologous stem cell transplant

2015 ◽  
Vol 57 (4) ◽  
pp. 973-976 ◽  
Author(s):  
Victor H. Jimenez-Zepeda ◽  
Peter Duggan ◽  
Paola Neri ◽  
Ahsan Chaudhry ◽  
Karen Murray ◽  
...  
Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1170-1170
Author(s):  
Rebecca L. Olin ◽  
David L. Porter ◽  
Selina M. Luger ◽  
Stephen J. Schuster ◽  
Donald Tsai ◽  
...  

Abstract Introduction: Autologous stem cell transplant (ASCT) as part of initial therapy has been shown to prolong survival of patients with multiple myeloma, with some achieving durable complete remission. However, the majority of patients ultimately relapse after ASCT and require salvage treatment. Options for the treatment of such patients have increased significantly over recent years, including not only novel chemotherapeutic and biological agents but also additional ASCTs. We performed a retrospective analysis of our experience with salvage ASCT for multiple myeloma to determine which clinical variables influence outcome. Methods: Between October 1992 and February 2005, we performed 342 ASCTs for multiple myeloma. Twenty-six of these were salvage transplants for relapsed disease after prior ASCT, and all were included in the analysis. Patients who received two planned (tandem) ASCTs were not included. Results: The median age at diagnosis was 47 (range 25–66), and median ISS and DS stages at diagnosis were 1 and 2, respectively. The initial ASCT was melphalan-based in 21/26; six (23%) achieved a complete response (CR) to the initial transplant, and fifteen (58%) achieved a partial response (PR). The median event-free survival (EFS) after the initial transplant was 19.5 months (range 2–60). The median time between initial and salvage ASCT was 2.6 years (range 0.3–7.6). Twenty-two patients (85%) received non-transplant therapy between ASCTs, and the median number of lines of therapy prior to salvage ASCT was 3. At the time of salvage ASCT, the median age was 52.5 (range 28–69). Fourteen patients received melphalan alone, eight received melphalan/TBI, and four received other regimens. Eleven patients (42%) achieved a response to therapy (1 CR, 10 PR). One patient (4%) died of transplant-related toxicity. The median follow-up after salvage ASCT is 12 months (range 0.2–58). Median EFS is 9 months, and median overall survival (OS) is 36 months. The 2-year EFS is 14%, and 2-year OS is 52%. On univariate analysis, both response to and EFS after initial transplant significantly predict improved EFS after salvage transplant (p=0.0008 and p=0.0065 respectively). Both also predict improved OS (p=0.03 and 0.0005 respectively). A greater than 12 month interval between first and second transplant also correlated with OS (p=0.04). There was no significant difference in EFS or OS by preparative regimen. Interestingly, type of response to the salvage transplant (CR/PR or less than PR) did not predict improved EFS or OS. Conclusion: This study suggests that salvage ASCT after relapse from initial ASCT is a feasible therapy for patients with heavily treated multiple myeloma, particularly those with a prolonged response to the first transplant.


2020 ◽  
Vol 13 (4) ◽  
pp. e233340
Author(s):  
Lee S Jamison ◽  
Clifton Craig Mo ◽  
Mary Kwok

In patients who experience relapse of multiple myeloma, upwards of 30% can have extramedullary disease. The presence of extramedullary multiple myeloma is typically associated with adverse cytogenetics and a poor prognosis. Organs most commonly involved include the liver, skin, central nervous system, pleural effusions, kidney, lymph nodes, and pancreas. We present the case of a 53-year-old man with IgA kappa multiple myeloma with the adverse cytogenetic findings of t(4;14) and 1q21 gain who had achieved a stringent complete (sCR) response after initial therapy with carfilzomib, lenalidomide and dexamethasone. Stringent complete response is defined as the normalization of the free light chain ratio in the serum and an absence of clonal cells in the bone marrow in additiion to criteria needed to achieve complete response. Prior to undergoing a planned autologous stem cell transplant, this patient experienced cardiac tamponade secondary to extramedullary relapse of his multiple myeloma which was limited to the pericardium. In response, his treatment regimen was transitioned to pomalidomide, bortezomib, dexamethasone and cyclophosphamide for three cycles after which he again achieved sCR and ultimately underwent autologous stem cell transplant. Post-transplant consolidation therapy was administered in the form of pomalidomide, bortezomib and dexamethasone, followed by pomalidomide and bortezomib maintenance, which he has continued to receive for 3 years without evidence of disease progression.


2014 ◽  
Vol 3 (4) ◽  
pp. 939-946 ◽  
Author(s):  
Lalit Kumar ◽  
Nida Iqbal ◽  
Anjali Mookerjee ◽  
Rakesh Kumar Verma ◽  
Om D. Sharma ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2042-2042
Author(s):  
Tomer M Mark ◽  
Whitney Reid ◽  
Ruben Niesvizky ◽  
Usama Gergis ◽  
Roger N Pearse ◽  
...  

Abstract Abstract 2042 Background: Given data showing efficacy of bendamustine in treating multiple myeloma (MM), with the known toxicity profile significant for myelosuppression, we hypothesized that the addition of bendamustine to autologous stem cell transplant (ASCT) conditioning would enhance response without significant toxicity change. We now report the results of a phase 1 study of bendamustine + melphalan conditioning ASCT in MM. Methods: 21 patients were enrolled onto a 3+3 phase 1 study of bendamustine added to melphalan 200mg/m2 split on subsequent days at the following dose levels on the indicated days of melphalan: 1) 30 mg/m2 given on day 2; 2) 60 mg/m2 on day 2; 3) 90 mg/m2 on day 2; 4) 60mg/m2 on days 1 and 2; 5) 90 mg/m2 on day 1 and 60mg/m2 on day 2; 6) 125 mg/m2 on day 1 and 100mg/m2 on day 2. Stem cell infusion of > 2 million × 106 CD34+ cells/kg was performed at 24–48 hours after final chemotherapy. Patients received G-CSF with standard supportive care until engraftment, defined as absolute neutrophil count > 500/ml and a platelet count > 20,000/ml. Bone marrow biopsy and skeletal imaging were prior to and 100 days after ASCT to assess baseline and post-ASCT disease status. Disease response evaluation was performed monthly with immunoelectrophoresis and free light chain analysis in accordance with international uniform myeloma reporting criteria. Results: Twenty-one patients completed ASCT over 6 cohorts: 3 in dose level 1, 6 at dose level 2, and 3 each in dose levels 3, 4, 5, and 6. Median number of days (range) to wbc engraftment and platelet engraftment was 11 (9–13) and 12.5 (10–22), respectively. Toxicities were graded according to the Bearman scale. There was only one Grade 3 toxicity: a patient with respiratory decompensation in the setting of neutropenic fever in cohort 2 (a pulmonary dose limiting toxicity-DLT). Other toxicities noted in patients (%) (Grade 1 / Grade 2 respectively) were Cardiac: 6 (29%) / 2 (10%); Pulmonary 1 (5%) / 1 (5%); CNS 0 / 1 (5%); Stomatitis 15 (71%) / 0; GI 10 (48%) / 1 (5%). The CNS toxicity was narcotic-related psychosis. Eight patients had neutropenic fever, with 3 cases of bacteremia. No transplant-related mortality occurred. At present, there are 18 evaluable Day +100 myeloma responses: disease progression in 5 (24%), stable disease in 1 (6%), partial response 1 (6%), very good partial response in 2 (11%), and complete response in 9 (50%). Four patients (19%) died from MM, all with disease progression at 100 days post-ASCT, and all with pre-existing extramedullary disease. Summary: Bendamustine added to ASCT conditioning in MM does not exacerbate expected toxicities. The maximum tolerated dose of bendamustine in combination with melphalan 200mg/m2 was not found after a series of 6 treatment cohorts. The relatively high complete response rate and good regimen tolerability has prompted an extension phase 2 trial at the cohort 6 dosing to further evaluate regimen efficacy. Disclosures: Off Label Use: The study evaluates bendamustine safety in transplantation for myeloma; there is no FDA-label for this. Niesvizky:Merck: Research Funding.


eJHaem ◽  
2021 ◽  
Author(s):  
Noa Biran ◽  
Wanting Zhai ◽  
Roxanne E. Jensen ◽  
Jeanne Mandelblatt ◽  
Susan Kumka ◽  
...  

2021 ◽  
Vol 21 ◽  
pp. S254
Author(s):  
Felipe Peña-Muñoz ◽  
Luz Román-Molano ◽  
Danylo Palomino-Mendoza ◽  
Alberto Hernández-Sánchez ◽  
Borja Puertas-Martínez ◽  
...  

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