scholarly journals Outcomes of relapse in patients with deferred autologous stem cell transplant after achieving at least very good partial response following bortezomib, adriamycin, dexamethasone chemotherapy for newly diagnosed multiple myeloma in the phase II PADIMAC trial

Author(s):  
Wei Yee Chan ◽  
Nicholas Counsell ◽  
Ruth Tute ◽  
Dunnya De‐Silva ◽  
Elizabeth H. Phillips ◽  
...  
2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8596-8596
Author(s):  
N. Shah ◽  
D. Weber ◽  
R. Orlowski ◽  
M. Wang ◽  
S. K. Thomas ◽  
...  

8596 Background: The introduction of novel therapeutic options with bortezomib and immunomodulatory agents in the up-front management of multiple myeloma (MM) has significantly improved induction response rates. However, the role of high dose chemotherapy and autologous stem cell transplant (ASCT) after induction with these highly active agents is not known, especially in patients with only a partial response to induction therapy. Methods: We conducted a retrospective review of 95 newly diagnosed MM patients treated with induction bortezomib-lenolidomide-dexamethasone (BLD) or bortezomib-thalidomide-dexamethasone (BTD) prior to ASCT. Responses were graded according to IMWG criteria. Results: 19 patients received BLD and 76 patients received BTD. All patients were conditioned with a melphalan-based regimen. Of the 19 patients who underwent induction with BLD, complete response (CR), very good partial response (VGPR) and partial response (PR) were achieved in 2 (11%), 8 (42%) and 9 (47%) respectively for an overall response rate (ORR) of 19/19 (100%). After ASCT, CR, VGPR and PR were achieved in 9 (47%), 5 (26%) and 5 (26%) respectively for a continued ORR of 21/21 (100%). Notably, 4/8 (50%) of patients with a VGPR after induction therapy with BLD improved to a CR after ASCT. 3/9 (33%) of patients with an initial PR to BLD improved to a CR and 1/9 (11%) with a PR improved to VGPR after ASCT. Of the 76 patients who underwent induction with BTD, CR, VGPR and PR were achieved in 6 (8%), 37 (49%) and 31(41%) respectively for an ORR of 74/76 (97%). 1 patient had stable disease and 1 patient had progressive disease. After ASCT, 27/76 (36%) achieved a CR, 30/76 (39%) a VGPR and 18/76 (24%) a PR for an ORR of 75/76 (99%). Of the patients who initially had a VGPR to BTD 16/37 (43%) improved to a CR while 5/32(16%)of PR patients improved to a CR and 9/32 (28%) of PR patients improved to a VGPR. Conclusions: Of the 40 patients who only achieved a PR after induction therapy with BLD or BTD, 16 (40%) had further improvement to a CR or VGPR after ASCT. Thus there is a significant benefit of ASCT in these patients who initially demonstrate relative resistance to induction therapy with highly active regimens. [Table: see text]


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5504-5504
Author(s):  
Eduardo Cervera ◽  
Jorge Carlos Torres ◽  
Nidia P. Zapata ◽  
Juan Rafael Labardini ◽  
Jose Ramiro Espinoza ◽  
...  

Abstract Introduction. Autologous stem cell transplant is considered the standard of care in young (<70) fit patients with Multiple Myeloma. We know that intensive chemotherapy or stem cell transplant do not produce a cure, but it does prolong event free survival and overall survival. The aim of this study is to report 15 years of experience in stem cell transplant at the Multiple Myeloma (MM) clinic at Instituto Nacional de Cancerologia (INCan). This is a retrospective, observational trial, we reviewed clinical and electronic files of patients that received an autologous stem cell transplant between January 1st of 2005 and March 1 2015. We assessed clinical status, demographic variables, disease status and clinical outcome of the patients that were included in the study. 48 patients were included into the study, 25 males and 23 females, we grouped the patients according to age, <35 years (2 patients), <50 years (14 patients), 50-65 years (31 patients), >65 years (1 patient). 34 patients had a normal karyotype, 4 had 13q14, 2 had MLL deletion and 8 did not had a karyotype performed. According to the M component we had 6 IgA patients, 32 IgG, 1 IgM, 1 Kappa, 5 lambda, 2 non secretory and 1 combined. According to ISS, 34 patients were assigned a ISS of 1, 10 a SS of 2, and 4 a ISS of 3. The majority of our patients were transplanted within the first line of treatment, 2 within the second line and none with more than 2 lines of treatment. 20 patients that received thalidomide plus dexamethasone achieved complete remission prior to transplant. 14 patients received thalidomide plus dexamethasone achieved very good partial response. 4 patients that received bortezomib plus thalidomide or dexamethasone achieved complete remission prior to transplant. 4 patients received bortezomib plus thalidomide or dexamethasone achieved very good partial response prior to transplant. 3 patients that received two lines of treatment achieved complete remission prior to transplant. 3 patients achieved very good partial response prior to transplant and received more than two lines of treatment. Time from diagnosis to transplant had a mean time of 17.4 months, with 6-12 months as the most prevalent group with 20 patients, followed with 13 patients in the 12-24 months window. 17 tandem transplants were performed. From the 25 patients that received a ASCT and were in CR, 19 maintained that response, from the 23 patients that achieved VGPR 20 maintained that response, 1 achieved partial response (PR), 4 had stable disease, and 4 had progression of the disease. We are looking forward to presenting the full data of our analysis. Since our casuistry does not differ from the international reports. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 445-445 ◽  
Author(s):  
Joseph R. Mikhael ◽  
Craig B. Reeder ◽  
Edward N. Libby ◽  
Luciano J. Costa ◽  
P. Leif Bergsagel ◽  
...  

Abstract Abstract 445 Background: Carfilzomib is a proteasome inhibitor that irreversibly binds its target and has a favorable toxicity profile that has shown significant activity in relapsed multiple myeloma (MM), leading to recent FDA accelerated approval. To achieve rapid and deep response in patients eligible for stem cell transplant, we combined carfilzomib with the regimen of cyclophosphamide-thalidomide-dexamethasone (CTD). We recently reported the results of the Phase I component of the trial (in which no MTD was reached) followed by the initial Phase II trial; however, with increasing evidence for the safe and effective use of higher doses of carfilzomib, we now report results from dose escalation extension of the Phase II trial. Methods: Newly diagnosed myeloma patients intended for stem cell transplant were eligible. All patients were treated on a 28 day cycle with Carfilzomib IV Days 1,2,8,9,15,16 (see Table 1 below for dosing per cohort) along with Cyclophosphamide 300 mg/m2 PO Days 1,8,15, Thalidomide 100 mg PO Days 1–28 and Dexamethasone 40 mg PO Days 1,8,15,22. We initially conducted a Phase I run in trial of 6 patients with no DLT observed before expanding to the Phase II portion of the study. The initial phase II regimen is shown below – as no DLTs were observed, we have now fully accrued to the Phase II dose level +1. Treatment was for 4 cycles with expected SCT post induction. The primary endpoint of the trial is the proportion of patients who have ≥very good partial response (VGPR) to treatment. All patients received herpes zoster prophylaxis and ASA daily. Results: A total of 38 patients have been accrued to the trial, 6 in the initial Phase 1, 21 in the initial Phase II, and the remaining at dose escalated cohorts. We are reporting the 27 patients who have completed therapy and will update with the dose escalated cohorts. Median age was 65 (range 27–74) and 52% were female. ISS Stage was advanced (II-III) in 56%. Best overall response rate during 4 cycles of CYCLONE at dose level 0 is 96%: CR 29%, VGPR 46%, PR 21% (1 pt achieved MR). Adverse events of grade 3 or higher at least possibly related to CYCLONE occurred in 12 (44%). Most commonly reported non hematological toxicities (all grades) included fatigue (67%), constipation (56%), lethargy (41%) somnolence (37%), malaise (30%) depressed level of consciousness (22%); however, grade 3/4 toxicities occurring in >5% were uncommon: thromboembolic event 11%) and muscle weakness (7%). Two cases of pneumonia required hospitalization. Eight patients (30%) developed grade 1 sensory neuropathy; no higher grade or painful neuropathy was evident. There were no cardiac events seen in greater than 5% of patients. Grade 3/4 hematological toxicities included neutropenia (15%) and lymphopenia (7%). All patients advancing to SCT successfully collected stem cells. One patient died on study from pneumonia. Conclusion: The 4 drug CYCLONE regimen is highly efficaceous with a response rate after only 4 cycles of 96% (75% ≥VGPR, 29% CR) at the current dosing level of carfilzomib IV 20/27 mg/m2 in newly diagnosed myeloma. Toxicities are manageable, with only grade 1 neuropathy and minimal cardiac or pulmonary toxicity. Increasing the dose of carfilzomib is feasible and updated results of dose escalated cohorts will be reported at 20/36 and 20/45 mg/m2. Disclosures: Bergsagel: onyx: Membership on an entity's Board of Directors or advisory committees. Stewart:Millennium Pharmaceuticals: Consultancy, Honoraria, Research Funding; Onyx: Consultancy; Celgene: Consultancy.


2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e20525-e20525 ◽  
Author(s):  
Tanya Marya Wildes ◽  
Sascha Alexander Tuchman ◽  
Brittany Depp ◽  
Ling Chen ◽  
Keith Stockerl-Goldstein ◽  
...  

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