Prolonged Survival Can be Achieved By Primary Plasma Cell Leukemia and Multiply-Refractory Multiple Myeloma Patients with Responding Disease Prior to Melphalan/Total Body Irradiation-Conditioned Myeloablative Allogeneic Hematopoietic Cell Transplantation

Background: Primary plasma cell leukemia (pPCL) and multiply-refractory multiple myeloma (MM) are plasma cell dyscrasias with a median survival of <1 year without aggressive treatment.  Prolonged remission can be achieved following allogeneic hematopoietic cell transplantation (alloHCT) in this population, although survival may be compromised by treatment-related mortality (TRM).  With the intention of providing long-term disease control, we have offered a myeloablative conditioning regimen containing melphalan 100 mg/m2 and 9 Gy of total body irradiation (MEL100/TBI9) followed by alloHCT to patients with these diseases. 

Methods: Seven patients with pPCL and 2 patients with multiply-refractory MM underwent MEL100/TBI9 alloHCT at the University of Pennsylvania between June 2009 and January 2013.  MEL was given as a single infusion of 100 mg/m2 on day -3 and TBI as 150 cGy twice daily on days -2, -1 and 0.  Palifermin was given on days -4 (60 mg/kg) and 0 (180 mg/kg) for prevention of mucositis.  Methotrexate and tacrolimus were used for graft-versus-host-disease (GVHD) prophylaxis.  Therapies pre- and post-alloHCT were given at the discretion of the treating physician.

Results: The median number of therapies pre- alloHCT was 3.5 (range 1-10) including bortezomib in 7 patients and high-dose melphalan in 2 patients.  Karnofsky Performance Status pre- alloHCT was <80 in 4 patients.  The median age at alloHCT was 48 years (range 42-57).  The donor source was a HLA-matched sibling in 5 patients and a 10/10 HLA-matched unrelated donor in 4 patients.  Disease response pre- alloHCT was very good partial response (VGPR) or better for 4 patients, partial response (PR) for 3 patients and stable disease/progressive disease (SD/PD) for 2 patients.  Lenalidomide maintenance was given post-alloHCT to 3 patients.  Acute GVHD of the intestine (3 patients; grade II, III and unknown) and skin (1 patient; grade II) as well as chronic GVHD of the oral cavity (2 patients; mild, moderate), skin (1 patient; moderate) and eyes (1 patient; moderate) was observed.   With a median length of follow-up of 31.6 months post-alloHCT (range 6.7-49.9) for patients surviving >100 days (n=6), the median event-free survival (EFS) was 28.2 months and the median overall survival (OS) was not yet reached.  As shown in Figure I, patients achieving VGPR or better prior to alloHCT experienced prolonged EFS and OS.  TRM was experienced by 3 patients (2 with SD/PD and 1 with PR pre-alloHCT), with all deaths occurring within approximately 30 days post-alloHCT due to sepsis.

Conclusions:  In pPCL and multiply-refractory MM patients demonstrating response to prior therapy, consolidation with MEL100/TBI9 alloHCT can result in long-term survival without severe toxicity.  MEL100/TBI9 should be analyzed prospectively either alone or in comparison to alternative alloHCT conditioning regimens in this patient population.