“I took the road less traveled, and that has made all the difference”: Making a case for high‐dose therapy and autologous stem cell transplantation in elderly patients with newly diagnosed multiple myeloma

Cancer ◽  
2021 ◽  
Author(s):  
Ajay K. Nooka ◽  
Nisha S. Joseph ◽  
Sagar Lonial
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Therapy ◽  
The Road ◽  
Difference Making ◽  
The Difference

Prognostic Impact of Chromosomal Abnormalities In Elderly Patients with Multiple Myeloma Treated with High-Dose Melphalan (MEL140) and Autologous Stem Cell Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1914-1914
Author(s):  
Peter Liebisch ◽  
Christian Straka ◽  
Hermann Einsele ◽  
Axel Hinke ◽  
Andreas Sandermann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Prognostic Significance ◽  
High Dose ◽  
Prognostic Impact ◽  
Newly Diagnosed

Abstract Abstract 1914 Background: Although chromosomal aberrations (CA) have emerged as important outcome predictors in multiple myeloma (MM), the prognostic significance of many recurring genomic changes is still unknown. Moreover, there is only scarce data on the implication of CA in elderly patients (pts.) receiving high-dose chemotherapy (HD-CTX) followed by autologous stem cell transplantation (ASCT). Aims: To evaluate the prognostic relevance of recurring CA as detected by cIg-FISH for elderly pts. with MM receiving HD-CTX and ASCT. Patients and Methods: Between 05/2001 and 08/2006, 549 pts. 60–70 yrs. of age with newly diagnosed symptomatic MM entered the DSMM II trial of the Deutsche Studiengruppe Multiples Myelom to receive two cycles of HD-CTX (melphalan 140 mg/sqm) followed by ASCT after 3–4 cycles of dexamethason-based induction chemotherapy (IC; arm A1) or no IC (arm A2). cIg-FISH and DNA probes mapping to chromosome bands 1p22, 1q21.2, 6q21, 8p11.2, 9q34, 11q25, 13q14, 14q32, 17p13, and 22q11 were applied to all pts. with sufficient bone marrow specimen at diagnosis. 289 pts. with a median age of 64 yrs. were included in the present analysis. Results: After a median follow-up of 82 weeks (w) the following CA were associated with a significantly shorter event-free survival (EFS): 17p13 deletion (17p–; 55 vs. 93 w, p<.0001); translocation t(4;14) (t(4;14); 65 vs. 95 w, p<.001), 1q21.2 gains (+1q21.2; 79 vs. 99 w, p=.0002); 13q14 deletion (13q–; 82 vs. 99 w, p=.03); and 8p11.2 deletion (8p–; 80 vs. 95 w, p=.04). Overall survival (OS) was significantly shorter in pts. with +1q21.2 (148 vs. 231 w, p<.0001); 17p– (118 vs. 219 w, p=.001); and t(4;14) (t(4;14); 195 vs. 223 w, p=.017). In a multivariable analysis t(4;14) (p<.001); 17p– (p=.0089); +1q21.2 (p=.031); and beta-2-microglobulin (p=.033) independently predicted outcome. Conclusion: In this large cohort of uniformly treated elderly pts. with newly diagnosed MM, CA – in particular 17p–, t(4;14), and +1q21.2 – remain strong predictive markers for outcome. Supported by a grant from the Else Kröner-Fresenius-Stiftung to P.L. and H.D. Disclosures: No relevant conflicts of interest to declare.

Sequential VAD (Vincristine, Adriamycin, Dexamethasone) and VTD (VELCADE®, Thalidomide, Dexamethasone) Induction Followed by High-Dose Therapy with Autologous Stem Cell Transplantation and Maintenance Treatment with VELCADE for Newly Diagnosed Multiple Myeloma: Interim Results of Phase II Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 952-952 ◽  
Author(s):  
Sung-Soo Yoon ◽  
Hye Jin Kim ◽  
Dong Soon Lee ◽  
Hyeon Seok Eom ◽  
Jun Ho Jang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Maintenance Treatment ◽  
Response Rate ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Newly Diagnosed

Abstract Introduction Effective reduction of myeloma before autologous stem cell transplantation (ASCT) prolongs survival in multiple myeloma patients. Recently, incorporation of novel agents resulted in improved response rate and reduced side effect in newly diagnosed multiple myeloma. Method: Patients are planned to receive 2 cycles of VAD (vincristine 0.4mg D1-4, adriamycin 9mg/m2 D1-4, dexamethasone 40mg D1-4, 9–12 every 3 weeks), and VTD (bortezomib 1.3mg/m2 D1, 4, 8, 11, thalidomide 100mg daily, dexamethasone 40mg D1-4, 9–12 every 3 weeks). High dose melphalan (200mg/m2) is used as a conditioning regimen for ASCT. Bortezomib (1.3mg/m2) as a maintenance treatment is administered weekly x 4 times every 6 weeks for 4 cycles after ASCT. Response was assessed by EBMT criteria, with additional category of nCR. Adverse events were graded by the NCI-CTCAE, Version 3.0. Result: At this interim analysis, 60 patients have been entered into the ongoing trial, and efficacy could be assessed in 53 patients. After 2 cycles of VAD, response rate was 70%. After VTD, two patients showed further improvement with additional CR, and an overall response was 97% with 14% CR. Especially, patients with poor prognostic cytogenetics (n=6) all responded after VTD. So far, autologous stem cells were successfully collected in all 28 patients with a median CD34+ count of 7.8 x 106/kg (range, 2.17–44.7 x 106/kg). In 24 patients who underwent autologous stem cell transplantation, five patients gained additional CR. There was no progression in patients completed bortezomib maintenance (n=9, CR 77%). The median follow-up duration was 6 months, median time to response was 1.4 months, and median overall survival was not reached. Grade 3,4 hematologic toxicity was more frequently observed after VAD than VTD (anemia 15.8%, 4.6%, neutropenia 7.9%, 3.5%), and incidence of grade 2,3 peripheral neuropathy was low (VAD 3.5%, VTD 7%). Conclusion: Sequential VAD and VTD induction therapy in newly diagnosed multiple myeloma was highly effective, even in patients with poor prognostic cytogenetics, and did not prejudice stem cell collection. VTD could have contributed to increased RR and minimized side effects. An updated results will be presented at the ASH meeting. *Protocol Number: KMM51-NCT00378755.

Sequential High-Dose Dexamethasone and Response Adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) Induction Chemotherapy Followed by High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma; Open-Labelled, Multicenter Phase 2 Study (KMM-94 Study)-Interim Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2044-2044
Author(s):  
Jin Seok Kim ◽  
Cheolwon Suh ◽  
June-Won Cheong ◽  
Kihyun Kim ◽  
Yang Soo Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Induction Chemotherapy ◽  
Induction Treatment ◽  
High Dose ◽  
Newly Diagnosed ◽  
Younger Patients ◽  
High Dose Dexamethasone

Abstract Abstract 2044 Background: Induction treatment followed by autologous stem cell transplantation (ASCT) is the standard therapy for the newly diagnosed younger patients with multiple myeloma (MM). Although new drugs such as lenalidomide or bortezomib have been shown the promising results as induction treatment, many different type of induction treatment regimens still have been used. We evaluate the efficacy and safety of the short course of high dose dexamethasone (HD dexa) and the response adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy in the newly diagnosed younger patients with MM. Methods: 107 newly diagnosed patients with MM from 21 institutions received 2nd cycles of HD dexa followed by PAD or VAD chemotherapy according to the response to the initial high dose dexamethasone. The primary endpoint was complete response (CR) + near CR rate after ASCT. Among 107 patents enrolled this study from November 2009, 25 patients (23%) have been dropped out. This trial will be continued until total 210 patients will be enrolled. The trial is registered on National Cancer Institute website, number NCT01255514. Results: One hundred seven patients (58 male, 49 female) were enrolled (median age; 56). 26 (24%) light chain disease were included. 31 (29%) patients were D-S stage II and 67 (63%) were stage III. According to the ISS, 23 (22%) patients had stage I, 51 (48%) had stage II and 33 (31%) had stage III. 26 (24%) patients had abnormal cytogenetics. There were 31% del13, 7% del17, 19% t(4;14), 15% t(14;16) and 28% t(11;14) in FISH analysis. Among the 82 evaluable patients, CR + PR rate was 48% (39/82) after 2nd cycles of HD dexa therapy. 39 patients (48%) received subsequent VAD chemotherapy and 43 patients (52%) received PAD chemotherapy. Among the 64 patients finished VAD or PAD chemotherapy, CR + PR rate was 83% (79%, 26/33 in VAD group vs. 87%, 27/31 in PAD group). 56 patients were finished ASCT until now. CR + near CR rate after ASCT were 61% (58% in VAD group vs 63% in PAD group). Mortality rate of this trial was 13% (11/82). The cause of death was disease progression (n=3), bleeding (n=1) and infections (n=7). Among 82 patients in whom VAD or PAD chemotherapy was actually performed, 1 year overall survival (OS) rate was 84.7%. 1 year survival rate was 93.8% versus 77.2% (P=0.049) with VAD versus PAD (median follow-up; 9.1 months). Conclusion: Risk adapted approach using initial steroid response showed good response results after ASCT compared with previous trial (CR + near CR rate of IFM 2005-01trial-Bortezomib+dexa induction & ASCT was 35%, J Clin Oncol. 2010;28:4621–9) The MM patients who had poor response to HD dexa also showed similar good response rate after ASCT compared with the patients who had good response to HD dexa treatment in this trial. PAD re-induction therapy after failure of initial steroid induction treatment might overcome the inferior results in the high risk MM patients. Therefore, initial steroid response adapted strategy might be the more cost-effective approach in the newly diagnosed ASCT eligible MM patients. Disclosures: No relevant conflicts of interest to declare.

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