Acute lymphoblastic leukaemia-type intensive chemotherapy to eliminate minimal residual disease after high-dose melphalan and autologous transplantation in multiple myeloma – a phase I/II feasibility and tolerance study of 17 patients

Powles, R; Sirohi, Bhawna; Kulkarni, Samar; Bhagwati, Niyati; Sašo, Radovan; Raje, Noopur; Horton, C; Singhal, Seema; Mehta, Jayesh; Treleaven, J

doi:10.1038/sj.bmt.1702379

Cited by 8 publications

(2 citation statements)

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“…26 C-VAMP has not been eliminated, but has been shifted to a later phase of therapy -and is administered as post-transplant consolidation based upon our prior observations of post-transplant intensive chemotherapy. 27 The idea is to see if the faster attainment of CR increases the proportion of patients remaining in remission long-term ('operational cure'). 28 In conclusion, patients with primary refractory myeloma should receive high-dose melphalan and undergo autotransplantation because a substantial proportion of them respond well and obtain survival benefit.…”

Section: Discussionmentioning

confidence: 99%

Response to induction chemotherapy is not essential to obtain survival benefit from high-dose melphalan and autotransplantation in myeloma

Singhal

Powles

Sirohi

et al. 2002

Bone Marrow Transplant

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Summary:Two hundred and twenty-two myeloma patients autografted after 200 mg/m 2 melphalan were studied to examine the relationship between response to induction chemotherapy and outcome. Induction comprised cyclophosphamide, vincristine, doxorubicin and methylprednisolone (C-VAMP) every 3 weeks for one cycle beyond maximum response. 81% responded to C-VAMP (chemosensitive) with 40 complete (CR) and 139 partial (PR) remissions, and 43 did not respond (NR; Ͻ50% reduction in paraprotein; primary refractory). Overall, 130 patients (59%) attained or remained in CR posttransplant; including 40% of NR, 53% of PR, and 97% of CR after C-VAMP (P Ͻ 0.0001). Amongst these 130 patients, the 5-year OS was independent of response to C-VAMP (NR 79%, PR 74%, CR 60%; P = 0.69). Similarly, among the 69 patients in PR post-transplant, the 5-year OS was independent of response to C-VAMP. In Cox analysis, lack of response to C-VAMP did not affect outcome significantly. These data show that lack of response to induction therapy does not automatically predict poor long-term outcome in myeloma, since a substantial proportion of these patients attain CR after autograft and enjoy extended survival. Myeloma patients should not be disqualified from an autograft based upon lack of response to induction chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Response to induction chemotherapy is not essential to obtain survival benefit from high-dose melphalan and autotransplantation in myeloma

Singhal

Powles

Sirohi

et al. 2002

Bone Marrow Transplant

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“…Thus, 20 clinical trials of newly diagnosed myeloma patients with information on MRD and clinical outcomes were identified and assessed for inclusion in this metaanalysis. Upon careful review of the 20 identified studies (12-14, 16, 18, 21, 58-71), four studies were excluded because they reported on ASCT (61-63, 71); seven were excluded because they did not evaluate the association between MRD status and PFS and/or OS (16,21,(64)(65)(66)(67)(68); four were excluded because they analyzed overlapping cohorts of patients (duplicates) (13,14,18,69); and one was excluded because the timing of MRD analysis was not specified (70). Four studies with information on MRD status and HR for PFS were included in the final analysis (12,(58)(59)(60).…”

Section: Mskcc/nci Meta-analysismentioning

confidence: 99%

The Role of Minimal Residual Disease Testing in Myeloma Treatment Selection and Drug Development: Current Value and Future Applications

Anderson

Auclair

Kelloff

et al. 2017

Clinical Cancer Research

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Treatment of myeloma has benefited from the introduction of more effective and better tolerated agents, improvements in supportive care, better understanding of disease biology, revision of diagnostic criteria, and new sensitive and specific tools for disease prognostication and management. Assessment of minimal residual disease (MRD) in response to therapy is one of these tools, as longer progression-free survival (PFS) is seen consistently among patients who have achieved MRD negativity. Current therapies lead to unprecedented frequency and depth of response, and next-generation flow and sequencing methods to measure MRD in bone marrow are in use and being developed with sensitivities in the range of 10 to 10 cells. These technologies may be combined with functional imaging to detect MRD outside of bone marrow. Moreover, immune profiling methods are being developed to better understand the immune environment in myeloma and response to immunomodulatory agents while methods for molecular profiling of myeloma cells and circulating DNA in blood are also emerging. With the continued development and standardization of these methodologies, MRD has high potential for use in gaining new drug approvals in myeloma. The FDA has outlined two pathways by which MRD could be qualified as a surrogate endpoint for clinical studies directed at obtaining accelerated approval for new myeloma drugs. Most importantly, better understanding of MRD should also contribute to better treatment monitoring. Potentially, MRD status could be used as a prognostic factor for making treatment decisions and for informing timing of therapeutic interventions. .

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Hematol. Oncol.

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Acute lymphoblastic leukaemia-type intensive chemotherapy to eliminate minimal residual disease after high-dose melphalan and autologous transplantation in multiple myeloma – a phase I/II feasibility and tolerance study of 17 patients

Abstract: The modern treatment of new patients with myeloma under the age of 75 years is increasingly involving initial courses of infusional chemotherapy with vincristine, an anthracycline and steroids (ie the C-VAMP programme) 1 followed

Cited by 8 publications

References 34 publications

Response to induction chemotherapy is not essential to obtain survival benefit from high-dose melphalan and autotransplantation in myeloma

Response to induction chemotherapy is not essential to obtain survival benefit from high-dose melphalan and autotransplantation in myeloma

The Role of Minimal Residual Disease Testing in Myeloma Treatment Selection and Drug Development: Current Value and Future Applications

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