Second Autologous Transplantation for Multiple Myeloma Patients Relapsing after the First Autograft – a Pilot Study for the Evaluation of Experimental Maintenance Therapies. Report of the Prospective Non-Randomized Pilot Study of the Czech Myeloma Group

Abstract

Background: High-dose chemotherapy followed by autologous stem cell transplantation (AT) is accepted as first-line therapy for patients with multiple myeloma (MM), with very good tolerance and low mortality (2–3%). Study Design: We tested repeated transplantation with different experimental maintenance therapies in patients with MM relapsing/progressing after first AT. Results were compared using intra-individual analyses, therefore inter-individual differences are excluded (T2 model). Patients and Methods: Between January 1997 and January 2003, 32 patients with relapsing/progressing MM after first AT were included in the pilot study, median follow-up was 75.2 months. They received the following experimental therapies: IL-2-activated PBSC (10 pts), pamidronate (4 pts), thalidomide (15 pts), consolidation chemotherapy CED (3 pts). Results: Sensitivity to C-VAD reinduction chemotherapy (4 cycles) was 50%, response to the second AT compared to the first was better in 7, the same in 16 and worse in 9 patients. Toxicity of the first and second transplantation was similar and usually did not exceed grade II (SWOG). Transplant-related mortality was 3% (1/32). Event-free survival after second AT (EFS II) is known in 22 patients; 7 have achieved prolongation of EFS II versus EFS I. In the whole group median EFS I was 15.7 months, median EFS II was 12.9 months, median overall survival (OS) was 79.1 months; 20/32 patients were alive at the time of analysis. Conclusions: Repeated AT is a feasible and successful strategy in treatment of relapsing MM; response to second AT and toxicity were acceptable and similar to the first AT in our assessment.

Treatment Options for Relapsed and Refractory Multiple Myeloma

“…Regimens based on conventional chemotherapy have included high-dose dexamethasone (18,19) (27), and then, further developed by Barlogie and colleagues, who showed that myeloablative doses of melphalan with appropriate hematopoietic stem cell support could overcome resistance to conventional-dose chemotherapy in this group of patients (28,29). Available data on second autologous transplants for relapsed patients suggest that these procedures are relatively well tolerated, with a 100-day mortality of <10% (30)(31)(32)(33). Recent studies using second salvage transplants include a sizeable proportion of patients who have received novel agents in the induction setting.…”

Soft-tissue extramedullary multiple myeloma prognosis is significantly worse in comparison to bone-related extramedullary relapse

“…Even in relapsed disease, remissions can be obtained in the majority of patients 4,5 although these tend to be shorter than first treatment responses. 6,7 Extramedullary myeloma is not frequent but is always associated with a significantly shorter overall survival, even in the era of novel agents. 3,[8][9][10][11][12] Extramedullary myeloma (EM) is a type of MM defined by the presence of extraskeletal (i.e.…”

Significance of salvage autologous stem cell transplantation (ASCT) for patients with multiple myeloma relapsing after up-front ASCT

“…GVHD responded promptly, and prednisolone was discontinued by salvage ASCT was ranged from 0% to 14.3%. 5,[7][8][9][10][11][12][13][14][15][16][17][18][19][20]22 So far, the outcomes of salvage ASCT in Japan have not been published. Accordingly, we aimed to conduct a retrospective study to clarify the outcome of ASCT and its significance on overall survival(OS)in patients with relapsed MM.…”

“…In Western countries, secondary ASCT with HD-MEL as a salvage therapy(salvage ASCT)for patients who have a relapse after up-font ASCT has been used in clinical practice. The median PFS after salvage ASCT ranged from 5 to 22 months, [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and the overall response rate ranged from 53.3 to 97.4%. 5,[7][8][9][10][11][12][13][14][15][17][18][19][20][21][22] The median treatment-related mortality rate associated with…”

“…4,5 To date, however, HHV6-associated pleurisy has not been recognized as a complication of HSCT. In this report, we describe an adult HSCT recipient who developed HHV6-associated pleurisy after an unrelated cord blood transplantation (CBT).…”