Prognostic factors for donor lymphocyte infusions following non-myeloablative allogeneic stem cell transplantation in multiple myeloma

Despite survival improvement with novel agents and use of autologous hematopoietic stem cell transplantation (HSCT), cure of patients with multiple myeloma (MM) remains anecdotal. Initial observations suggested that chronic GvHD was accompanied by an anti-myeloma effect after myeloablative HSCT, but unfortunately this procedure was hampered by high non-relapse mortality (NRM). To maximize the anti-myeloma effect and minimize NRM, we developed a non-myeloablative (NMA) regimen associated with a high incidence of chronic GvHD and tested its efficacy on patient survival and disease eradication. From 2001 to 2010, 92 patients aged ⩽ 65 years with a compatible sibling donor received autologous HSCT followed by an outpatient NMA allogeneic HSCT using a conditioning of fludarabine and cyclophosphamide. Patient median age was 52 years and 97% presented DurieSalmon stages II-III disease. After a median follow-up of 8.8 years, probability of 10-year progression free and overall survival were 41% and 62%, respectively. Although the cumulative incidence of extensive chronic GvHD was high (at 79%), the majority of longterm survivors were off immunosuppressive drugs by year 5 and NRM was low (at 10%). Together, our results suggest that potential MM cure can be achieved with NMA transplantation regimens that maximize graft-versus-myeloma effect and minimize NRM.

Section: Introductionmentioning

confidence: 99%

Favorable long-term outcome of patients with multiple myeloma using a frontline tandem approach with autologous and non-myeloablative allogeneic transplantation

Ahmad

LeBlanc

Cohen

et al. 2015

“…Donor lymphocyte infusion (DLI) with T cells has become an established and commonly adopted modality in the management of relapse in such a setting, with the greatest efficacy observed in relapsed CML. 1,2 Graft vs tumour effect augmented by donor T cells has also been demonstrated in low grade lymphoma, 3 CLL, 3 Hodgkin's disease (HD), 4 as well as multiple myeloma, 5,6 and to a lesser extent in AML, myelodysplastic syndrome and ALL. 7 For NK cells, the rapidly accumulating knowledge over the past few years has facilitated clinical studies, exploiting the alloreactivity of donor NK cell infusion in the prevention and treatment of relapse in a non-transplant setting.…”

Section: Introductionmentioning

confidence: 99%

The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies

Niam

et al. 2011

We performed a Phase I/II clinical trial to study the feasibility, toxicity and efficacy of allogeneic cytokineinduced killer (CIK) cell expansion, and treatment for patients with haematological malignancies who relapsed after allogeneic haemopoietic SCT (allo-HSCT). Allogeneic CIK cells were successfully generated for a total of 24 patients, including those from patients' own leukapheresis products in 5 patients who had no access to further donor cells. The median CD3 þ T-cell expansion was 9.33 (1.3-38.97) fold, and CD3 þ CD56 þ natural killer (NK)-like T-cell expansion was 27.77 (2.59-438.93) fold. A total of 55 infusions were done for 16 patients who had either failed or progressed after initial response to various individualized chemotherapy regimens and donor lymphocyte infusion (DLI), at doses ranging from 10 to 200 million CD3 þ cells/kg. Response attributable to CIK cell infusion was observed in five patients. These included two with ALL, two with Hodgkin's disease (HD) and one with AML, and two of whom had a response sustained for more than 2 years. Acute GVHD occurred in three and was easily treatable. This study provides some evidence suggestive of the efficacy of allogeneic CIK cells even after failure of DLI in some cases.

“…53 There is limited data regarding the use of bortezomib in this setting. In a small study, two cycles of four doses were completed by 14 patients, 55 with neurotoxicity and thrombocytopenia being the most frequently reported adverse events and in four patients there might have been some stimulation of GVHD. Nonetheless, complete and partial response rates of 30 and 50% were promising outcomes.…”

Section: Is Allosct the Penultimate Intervention? Post-allosct Therapymentioning

confidence: 99%

In pursuit of the allo-immune response in multiple myeloma: where do we go from here?

Cook

Bird

Marks

2008

AlloSCT is a potentially curative procedure for haematological malignancies and marrow failure syndromes. However, unlike leukaemia and lymphoproliferative disorders, AlloSCT has yet to find its place in the clinical management of patients with multiple myeloma. AlloSCT in multiple myeloma is associated with a high procedurerelated mortality (TRM up to 35%) when full-intensity conditioning is used and only up to 36% of cases show long-term disease-free survival. The introduction of reduced intensity conditioning AlloSCT, more recently following an autologous SCT, has reduced the TRM to o20%, but there is an associated increased relapse risk. The use of donor lymphocyte infusions and novel biological agents (thalidomide, bortezomib), alone or together, can be effective in relapsed and even persistent disease post-AlloSCT. Thus, in pursuit of the putative graft-versus-myeloma effect, we need to consider the whole patient management pathway both preceding (depth of response to novel agents) and post-AlloSCT, to minimize the toxicity while harnessing the adoptive immunotherapy effect. This review sets out what we have learned to date from the clinical research studies in this area, examines concepts for improving the outcomes of AlloSCT and proposes a potential direction of clinical investigation to maximize the effect of AlloSCT in multiple myeloma.