Impact of High-Risk Cytogenetics and Achievement of Molecular Remission on Long-Term Freedom from Disease after Autologous–Allogeneic Tandem Transplantation in Patients with Multiple Myeloma

Abstract

Within a prospective protocol, the incidence and impact of achievement of molecular remission (mCR) and high-risk cytogenetics was investigated in 73 patients with multiple myeloma (MM) after autologous (auto)-allogeneic (allo) tandem stem cell transplantation (SCT). After induction chemotherapy, patients received melphalan 200 mg/m(2) before undergoing auto-SCT, followed 3 months later by melphalan 140 mg/m(2) and fludarabine 180 mg/m(2) before allo-SCT. Sixteen patients had high-risk cytogenetic features, defined by positive FISH for del(17p13) and/or t(4;14). Overall, 66% of the patients achieved CR or near-CR, and 41% achieved mCR, which was sustained negative (at least 4 consecutive samples negative) in 15 patients (21%), with no significant difference in incidence between the patients with high-risk cytogenetics and others (P = .70). After a median follow-up of 6 years, overall 5-year progression-free survival was 29%, with no significant difference between del 17p13/t(4;14)-harboring patients and others (24% versus 30%; P = .70). The 5-year progression-free survival differed substantially according to the achieved remission: 17% for partial remission, 41% for CR, 57% for mCR, and 85% for sustained mCR. These results suggest that auto-allo tandem SCT may overcome the negative prognostic effect of del(17p13) and/or t(4;14) and that achievement of molecular remission resulted in long-term freedom from disease.

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

“…To date, it remains uncertain whether a tandem approach can overcome poor risk factors, albeit there is some evidence in the literature that allogeneic transplant might have a positive impact in patients presenting with high-risk cytogenetics. 20,35,43,44 In summary, over 40% of our 92 patients are long-term survivors without evidence of progression after a median follow-up of 8.8 years and may be cured. Our data add further support to the evidence of a sustainable GvMM effect potentially able to cure a subset of patients.…”

Allogeneic hematopoietic cell transplantation for multiple myeloma in Europe: trends and outcomes over 25 years. A study by the EBMT Chronic Malignancies Working Party

“…41,42 Although remission rates before and after transplantation are important, the use of molecular evaluation of minimal-residual disease has been demonstrated to have a highly significant impact on disease recurrence detection, where an immediate therapeutic intervention could offer a low-risk opportunity to extend the duration of remission and survival. 43,44,45 Considering the poor outcome for high-risk patients, that is, those with the del(17p), gain(1q), t(4;14) and t(14;16) abnormalities, with current treatments, studies of upfront auto-RIC-allo-HSCT, including novel drugs, are warranted in such high-risk young patients. Previous prospective and retrospective reports evaluating allo-HSCT in MM, in the majority of cases, high-risk patients were classified mainly according to beta2 microglobulin and del(13q) that in absence of other poor prognostic abnormalities is no longer considered as a high-risk feature.…”

Stem cell transplantation in multiple myeloma and other plasma cell disorders (report from an EBMT preceptorship meeting)

“…Some phase II trials evaluating these concepts have been performed. [45,[47][48][49][50][51][52] Further evidence of a synergism between new drugs and donor T cells has recently been shown in a comparative study in newly diagnosed patients, where higher response rates to salvage therapies with new drugs were observed in the allo-SCT patients. This translated into significantly longer OS from relapse after the allo-SCT, compared to a second auto-SCT [ Figure 2].…”