Treatment Pattern and Overall Survival in Newly Diagnosed Multiple Myeloma Patients who are not Eligible for Autologous Stem Cell Transplantation

Purpose We performed a prospective, randomized study of single (arm A) versus double (arm B) autologous stem-cell transplantation (ASCT) for younger patients with newly diagnosed multiple myeloma (MM). Patients and Methods A total of 321 patients were enrolled onto the study and were randomly assigned to receive either a single course of high-dose melphalan at 200 mg/m2 (arm A) or melphalan at 200 mg/m2 followed, after 3 to 6 months, by melphalan at 120 mg/m2 and busulfan at 12 mg/kilogram (arm B). Results As compared with assignment to the single-transplantation group (n = 163 patients), random assignment to receive double ASCT (n = 158 patients) significantly increased the probability to attain at least a near complete response (nCR; 33% v 47%, respectively; P = .008), prolonged relapse-free survival (RFS) duration of 18 months (median, 24 v 42 months, respectively; P < .001), and significantly extended event-free survival (EFS; median, 23 v 35 months, respectively; P = .001). Administration of a second transplantation and of novel agents for treating sequential relapses in up to 50% of patients randomly assigned to receive a single ASCT likely contributed to prolong the survival duration of the whole group, whose 7-year rate (46%) was similar to that of the double-transplantation group (43%; P = .90). Transplantation-related mortality was 3% in arm A and 4% in arm B (P = .70). Conclusion In comparison with a single ASCT as up-front therapy for newly diagnosed MM, double ASCT effected superior CR or nCR rate, RFS, and EFS, but failed to significantly prolong overall survival. Benefits offered by double ASCT were particularly evident among patients who failed at least nCR after one autotransplantation.

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Phase 2 randomized study of daratumumab (dara), lenalidomide (R), bortezomib (V), and dexamethasone (d; Dara-RVd) vs. RVd in patients (pts) with newly diagnosed multiple myeloma (MM) eligible for high-dose therapy (HDT) and autologous stem cell transplantation (ASCT)

Annals of Oncology ◽

10.1093/annonc/mdx373.044 ◽

2017 ◽

Vol 28 ◽

pp. v369

Author(s):

T. Lin ◽

L. Hydutsky ◽

H. Parros ◽

S. Murphy ◽

H. Pei ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Randomized Study ◽

High Dose ◽

Phase 2 ◽

Newly Diagnosed ◽

High Dose Therapy

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Patient-Reported Outcome Results From the Open-Label, Randomized Phase III Myeloma X Trial Evaluating Salvage Autologous Stem-Cell Transplantation in Relapsed Multiple Myeloma

Journal of Clinical Oncology ◽

10.1200/jco.18.01006 ◽

2019 ◽

Vol 37 (19) ◽

pp. 1617-1628 ◽

Cited By ~ 7

Author(s):

Sam H. Ahmedzai ◽

John A. Snowden ◽

Andrew John Ashcroft ◽

David Allan Cairns ◽

Cathy Williams ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Adverse Effects ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Random Assignment ◽

Time To Progression ◽

Patient Reported

PURPOSE Salvage autologous stem-cell transplantation (sASCT) in patients with multiple myeloma (MM) relapsing after a prior autologous stem-cell transplantation leads to increased remission duration and overall survival. We report a comprehensive study on patient-reported outcomes, including quality of life (QoL) and pain in sASCT. METHODS Patients were randomly assigned to either sASCT or nontransplantation consolidation (NTC). Pain and QoL were assessed as secondary outcomes using validated QoL instruments (European Organisation for Research and Treatment of Cancer QLQ-C30 and myeloma-specific module, QLQ-MY20; the Brief Pain Inventory [Short Form]; and the Leeds Assessment of Neuropathic Symptoms and Signs [Self-Assessment] scale). RESULTS A total of 288 patients (> 96%) consented to the QoL substudy. The median follow-up was 52 months. The European Organisation for Research and Treatment of Cancer QLQ-C30 Global health status scores were higher (better) in the NTC group at 100 days after random assignment ( P = .0496), but not at later time points. Pain interference was higher (worse) in the sASCT group than in the NTC group at 6 months after random assignment ( P = .0267), with patients with sASCT reporting higher scores for Pain interference with daily living for up to 2 years after random assignment. Patients reporting lower concerns about adverse effects of treatment after sASCT had a time to progression advantage. CONCLUSION Patients with sASCT with relapsed MM demonstrated a comparative reduction in QoL and greater impact of treatment adverse effects lasting for 6 months and up to 2 years for pain, after which patients who had received sASCT reported better outcomes. Patients who experienced lower adverse effects after sASCT had longer time to progression and overall survival, showing the need to improve symptom management peritransplantation. To our knowledge, this study provides the most comprehensive picture of QoL before and after sASCT in patients with relapsed MM.

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Up-Front Therapy for Multiple Myeloma: A Survey of Practice Patterns in the USA.

Blood ◽

10.1182/blood.v106.11.5172.5172 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5172-5172

Author(s):

Kavita Natarajan ◽

Gary H. Lyman ◽

Oscar F. Ballester

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Initial Therapy ◽

Newly Diagnosed ◽

The Usa ◽

Choice Of Therapy

Abstract Introduction: Several treatment programs are available for the initial management of patients with multiple myeloma, with no clear documented advantage(s) of one regimen over the others in terms of time to progression (TTP) or overall survival (OS). Materials and Methods: A questionnaire was mailed to 540 randomly selected members of ASH during early 2005. Practitioners were asked their choice of therapy for newly diagnosed myeloma patients during 2004, based on 2005 NCCN guidelines, including: 1) melphalan/prednisone (MP), 2) vincristine / adriamycin / decadron (VAD), 3) high-dose decadron (HD), 4) thalidomide / decadron (Thal/Dex), 5) doxyl / vincristine / decadron (DVD); the options of a clinical trial (CT) or “other” were also included. Physicians were asked about factors influencing their choice of therapy for individual patients and their recommendations for autologous stem cell transplantation as part of the initial treatment schema. Results: Surveys were returned by 123 physicians(19.2%), of which 93 contained evaluable data. Among responders, 52% were in private practice and 47% in academic institutions and 74% respondants reporting having been in practice for more than 10 years. A large majority of physicians (74%) utilized 3 or more different regimens, only 10.7% of responders used a single regimen for all of their patients. Thal/Dex was used by 87% of responders, with 47% of them recommending this regimen in ≥ 50% of their patients. MP, HD and VAD were used by 67.7%, 49% and 44% of responders, but only 10.7%, 4% and 3% respectively, recommended them to ≥ 50% of their patients. DVD was used by 25% of physicians. Of respondants, 64.5% did not accrued patients to clinical trials and only 7.5% of physicians accrued ≥ 50% of their patients to clinical trials. No significant differences in the choice of regimen were apparent based on years of practice. Physicians in academic centers tended to use HD (p =.002) and accrue patients to CT (p=. 001) more often than those in private practice. Factors identified as important in selecting initial therapy for individual patients included: age (92%); performance status (95%); prognostic factors, such as β2-microglobulin and cytogenetics (75%); and candidacy for stem cell transplantation (93%). Respondants consider autologous stem cell transplantation as part of the initial therapy for all eligible patients (47%), only those with responsive disease (42%) and normal renal function (30%); only in selected cases (76%). Conclusions: Thal/Dex appears to be currently the most commonly recommended up-front therapy for multiple myeloma in the USA, in spite of the lack of published data documenting patient benefit in terms of TTP and OS. A sizable proportion of physicians do not recommend autologous stem cell transplantation as part of the initial therapy of newly diagnosed myeloma patients despite confirmed randomized clinical trials documenting benefit.

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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 ◽

10.1182/blood.v110.11.952.952 ◽

2007 ◽

Vol 110 (11) ◽

pp. 952-952 ◽

Cited By ~ 3

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.

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Third Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma

Blood ◽

10.1182/blood.v120.21.4548.4548 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4548-4548

Author(s):

Catherine Garnett ◽

Chrissy Giles ◽

Maialen Lasa ◽

Osman Ahmed ◽

Marco Bua ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Disease Progression ◽

Cell Transplantation ◽

Median Time ◽

Autologous Stem Cell Transplantation ◽

Autologous Stem Cell Transplant ◽

Cell Transplant

Abstract Abstract 4548 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma (MM). In the face of almost inevitable disease relapse, there is growing evidence for second ASCT as salvage therapy in certain patient groups. However, few published data exist regarding efficacy and safety of third ASCT in relapsed disease. We retrospectively analysed the results of eight patients treated at a single UK institution who each received three separate autologous stem cell transplants for relapsed MM between May 1997 and April 2012. There were four men and four women. Median age at diagnosis was 48 years (range, 25–64 years). Paraprotein isotype was IgA in two patients and IgG in the remaining six patients. At the time of 1st transplant, seven patients were in partial response (PR) and one in complete response (CR). Conditioning melphalan dose was 200mg/m2 in all but two patients who received 140mg/m2. Three patients entered CR following 1st transplant and four patients showed PR. Median time to disease progression was 31 months (range, 11.8–52.9 months). Prior to 2nd transplant, five patients achieved very good partial response (VGPR) and three PR with induction chemotherapy. Melphalan dose was 200mg/m2 in five patients and 140mg/m2 in the remaining three. Median time to disease progression was 22.3 months (range, 10.1– 39.6 months). At the time of 3rd transplant, two patients had achieved VGPR following induction chemotherapy, one showed PR, two stable disease (SD) and three evidence of disease progression. For the 3rd transplant, melphalan dose was reduced in most cases. Median follow up post 3rd transplant was 8.3 months (range 1.1–29.3 months). One patient died of overwhelming sepsis within one month of transplantation (treatment related mortality). At the time of analysis, five patients had relapsed following 3rd ASCT, with median time to disease progression of 10.4 months (range, 2.7–23.7 months). Three of these patients died at 3.5, 17.6 and 27.1 months post 3rd transplant. The remaining two patients are alive with no evidence of disease relapse (progression free survival (PFS) time of 3.3 and 1.3 months). Overall survival (OS) for the group from diagnosis is 62% at 10 years with a median OS from diagnosis of 149 months (range 68.5 – 189.2 months) (Figure 1). Median OS for the group from 3rd transplant is 17.6 months (range, 1.1–29.3 months) (Figure 2). Median PFS is 10.4 months (range 1.1–23.7 months). These results demonstrate that third ASCT is a possible treatment strategy for patients with relapsed MM and may prolong patient survival. Figure 1: Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 1:. Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 2: Overall survival from time of 3rd autologous stem cell transplant Figure 2:. Overall survival from time of 3rd autologous stem cell transplant Disclosures: No relevant conflicts of interest to declare.

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