ALL-346 Acute Lymphoblastic Leukemia Following Multiple Myeloma Therapy: A Single-Center Experience With 9 Patients

Background: Patients with multiple myeloma (MM) have an increased risk of developing second malignancies, especially myeloid neoplasms (t-MDS/AML). However, little is known about the occurrence of lymphoid malignancies, in particular acute lymphoblastic leukemias (ALLs). Methods: We retrospectively analyzed the disease characteristics and outcomes of patients diagnosed with ALL following MM who presented to the MD Anderson Cancer Center between 2005 and 2018. Results: A total of 9 patients were identified. The majority of patients were female (88%). The median age at the time of MM diagnosis was 67 years (range, 48–74) and 75 years (range, 54–85) at the time of diagnosis of ALL. All patients were receiving lenalidomide as part of MM therapy when they developed ALL. The median time from the diagnosis of MM to ALL diagnosis was 6.8 years (range, 0.33–9.86). All patients were diagnosed with Philadelphia chromosome–negative B-ALL, with a median blast percentage in the bone marrow of 83% (range, 45–100). Of the 9 patients, 3 had complex karyotype with monosomy 13/trisomy 4,5,9,15, 4 patients had a detected mutation of TP53, and 1 patient showed MLL rearrangement. Treatment of B-ALL consisted of a mini-hyper-CVD regimen (n=3) or mini-hyper-CVD + inotuzumab (n=6); 6 patients received blinatumomab as part of the consolidation therapy. Eight patients achieved CR after induction therapy. All patients during ALL diagnosis were MM free; however, 1 patient relapsed with MM after completion of ALL therapy. The median OS from the time of ALL diagnosis was 2.7 years (range, 0.46–5.21). Conclusions: B-ALL can occur in patients with MM with a median latency of 6.8 years. All patients were receiving lenalidomide at the time of diagnosis of ALL. All patients in our series had Ph-neg B-ALL, and 4/9 had a concomitant TP53 mutation.