Prior studies have shown that myeloma patients exhibiting either genetically defined high-risk disease or plasma cell leukemia have a poor outcome with a median overall survival (OS) of ≤3 years. Results of IFM 2005-01 and 02 suggest that relatively limited bortezomib-containing induction regimens did not produce a major survival benefit among these patients. However, results of recent studies suggest that combination therapy may benefit these patients when given early and again later in the treatment. We evaluated a combination maintenance/consolidation regimen (RVD) following autologous stem cell transplant (ASCT) for high-risk patients to evaluate the impact of this approach on outcome. Following initiation of RVD maintenance, 51% of patients achieved stringent complete response (sCR), with 96% achieving at least VGPR as best response. Median progression free survival (PFS) for all patients is 32 months with a 3-year OS of 93%. The regimen was well tolerated with no grade 3/4 neuropathy. Early ASCT followed by RVD maintenance is a promising strategy for high-risk myeloma patients and delivered excellent response rates, and promising PFS and OS.

Reduced-intensity conditioning (RIC) permits allogeneic hematopoietic progenitor cell transplantation in patients who would not be considered candidates for transplantation using a myeloablative preparative regimen because of age, comorbidities or prior therapy. In the setting of myeloablative transplantation, use of antithymocyte globulin (ATG) can reduce the risk of GVHD without negatively affecting transplant outcomes; however, limited data exist on the impact of ATG in the setting of RIC, particularly when there is HLA-mismatch. We performed a retrospective analysis of 85 patients who received unrelated donor transplants at our institution for hematologic malignancies following conditioning with fludarabine and melphalan (FluMel), with or without rabbit ATG (6 mg/kg). ATG was targeted to patients receiving HLA-mismatched grafts. With a median follow-up of 36 months, those receiving ATG and a mismatched graft had similar rates of acute and chronic GVHD, relapse, and similar OS compared with those receiving HLA-matched grafts without ATG. In a multivariate analysis, HLA-mismatched donor was not associated with a decrement in OS. We conclude that this intermediate dose of ATG is effective in preventing severe GVHD in the setting of HLA-mismatch, without undue compromise of the graft versus tumor effects on which RIC transplants depend.

8100 Background: Despite markedly improved survival rates for MM pts in the last decade, 15-20% of pts with high risk genetics continue to have dismal outcomes with a median PFS of 18.5 months (Kapoor P et al). In this subset of pts, efforts are needed to improve response rates and prolong the response duration, but doing so without genotoxic therapy as this has been shown not to improve outcomes (Barlogie et al). Methods: We evaluated 37 pts with high risk features [del17p (n=16), t(4;14) (n=1), t(14;16) (n=4) by FISH/CTG; hypodiploidy (n=9), del 13 (n=16); complex karyotype (n=14) by CTG; PCL (n=7) and atypical presentation (n=4)]. After completing induction therapy, all pts underwent ASCT followed by RVD maintenance. 60 days after ASCT following hematological recovery, pts began maintenance [lenalidomide 10 mg/day (days1–21), bortezomib 1.3 mg/m2 and dexamethasone 40 mg once a week (days 1, 8, 15) every 28 days]. Results: The response rates are summarized in the table. 7/36 pts progressed while on RVD maintenance. The median PFS and OS for pts on RVD maintenance has not been reached. Pts with <VGPR pre-ASCT and with <VGPR on RVD maintenance have median PFS of 28 months and 11 months, respectively. 4 pts with prior h/o DVT received anticoagulation, while all others received ASA for DVT prophylaxis. No thrombotic events were seen. There were no grade 3/4 toxicities or treatment-related mortality. The most common toxicities during maintenance schedule were: PN-40% (G1: 26%; G2:14%); G1 rash-10% and G1 fatigue in 78% pts. Cytopenias were seen in 25% pts and dose reductions were made in 50% pts. There is no report of secondary malignancies. Conclusions: Early ASCT followed by RVD maintenance delivers superior response rates in this high risk segment achieving sCR in 47% and ≥VGPR in 73% pts and prevents early relapses. The median PFS and OS have not been reached. RVD maintenance regimen is well tolerated and promising. [Table: see text]

No abstract

8540 Background: Lenalidomide, bortezomib and dexamethasone (RVD) is an active, tolerable induction regimen with superior response rates (≥VGPR rates of 80%) in newly diagnosed MM pts. However, the optimal timing of ASCT with this triplet combination is uncertain. We have evaluated our institutional experience to provide an insight for the best timing of ASCT, where specific patients were offered delayed ASCT based on risk, response and toxicity of therapy. Methods: 222 consecutive transplant-eligible pts with newly diagnosed MM that received at least 3 cycles of RVD and harvested stem cells were included in the analysis from May 2007 until October 2011. Patients underwent early ASCT (received planned ASCT immediately after stem cell harvest, n=136) or delayed transplant (received planned maintenance therapy after collection with intent to proceed with ASCT at first relapse, n=86). Results: Median age of the patients at the time of diagnosis is 60.5 yrs (32-77) vs. 60 yrs (22-73) for early vs. delayed groups. ISS stage 3 disease was seen in 31% patients and 10% patients; high risk cytogenetics were seen in 11% and 7% patients in early vs. delayed groups, respectively. Median time from initiation of induction therapy to ASCT in early group is 5.45 months (range, 3.19-12.68 months). In the delayed SCT group, 28 patients underwent ASCT at a median time of 26.21 months (range, 13.67-41.72 months) from initiation of therapy. At a median follow up of 32 months, 5-year overall survival from diagnosis was 68% and 88% in patients undergoing early and delayed ASCT, respectively (p = 0.106). Conclusions: Transplantation-eligible patients who receive RVD as initial therapy followed by early vs. delayed ASCT result in comparable overall survival. In carefully selected newly diagnosed myeloma patients with lower ISS stage receiving RVD as induction therapy, planned delayed ASCT results in 5-year survival rates close to 90%.