LAUSR

The incidence of patients with multiple myeloma (MM) followed by hematologic malignancies as second primary malignancy is around 0.8 – 3.1%. The majority of cases are myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), however, acute lymphoblastic or mixed phenotype leukemia can be rarely observed. A retrospective chart review was performed for patients diagnosed with acute lymphoblastic or mixed phenotype leukemia from January 2009 through February 2020. Two patients were identified and the corresponding clinical data were reviewed. Case 1 was a 74-year old male diagnosed with pre-B ALL 5 years after an IgG Lambda MM. His MM therapy included Bortezomib-based chemotherapy followed by Lenalidomide maintenance. Pre-B diagnosis was confirmed on a pelvic lesion biopsy with sheets of intermediate sized cells (CD45+, PAX5+, CD34+, CD43+, CD10+, BCL6+ and BCL2+). The patient had 4 cycles of HyperCVAD chemotherapy, followed by Blinatumomab and Inotuzumab treatment. Unfortunately, the patient was referred to hospice 2 years after the diagnosis of ALL. Case 2 was a 69-year old male diagnosed with mixed phenotype acute leukemia 8 years after an lgA Lambda MM with del 13q and Trisomy 11. The patient was treated with Bortezomib-based chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) and Lenalidomide maintenance. Bone marrow biopsy showed around 79% blasts (CD34+, PAX-5+, CD79a+ and MPO+). Flow cytometry from bone marrow showed 90% precursor B cells, however MPO was negative. Furthermore, a DNTM3A p.T835M missense variant (25-30% fraction) was identified by next generation sequencing (NGS). The patient was scheduled for Hyper-CVAD chemotherapy. Lenalidomide maintenance following auto-HSCT is considered a standard therapy for MM patients. Recent studies indicate that Lenalidomide maintenance is associated with an increased risk of second primary hematologic malignancies. Although AML and MDS are more commonly seen, ALL and rarely mixed phenotype leukemias can occur.