CD19-Targeted CAR T Cell Therapy for Concomitant Diffuse Large B Cell Lymphoma and Myeloma

While DLBCL and myeloma comprise a large fraction of annual hematologic malignancies, the co-occurrence of these malignancies is particularly rare. The FDA has approved three CD19-targeted CAR T cell therapies for B-cell lymphoma (Kymriah, Yescarta, and Brenyazi) and more recently a single CAR T cell therapy for myeloma (Abecma). We present a case of concurrent multiply r/r DLBCL and non-r/r myeloma treated exclusively with CD19-targeted CAR T cell therapy. A 77-year-old female was admitted to an outside hospital with a chief complaint of one week of constipation, incidental labs demonstrating hypercalcemia and AKI, and a bone marrow biopsy consistent with myeloma (phenotype lamda, CD138-, MUM01+, CD56- and CD117, KITE-). There were 20% lambda-restricted plasma cells with no evidence of lymphoma. She also had concomitant anemia with a hemoglobin of 9.6 g/dL best attributed to the plasma cell dyscrasia, thus fulfilling criteria from the International Myeloma Working Group.Beta-2-microglobulin was 6.8 mg/L, consistent with stage 3 disease. She demonstrated two M proteins at time of diagnosis; each was 0.40 g/dL. Interestingly these monoclonal proteins were IgG-Kappa and an IgM protein. The patient was transferred to our institution for management after receiving a single cycle of bortezomib, cyclophosphamide and dexamethasone. A right inguinal lymph node biopsy of an existing right thigh mass revealed atypical cells with findings consistent with non-GC DLBCL [CD20+, PAX5+ (weak), MUM1+, BCL2+, CD10-, CD5-, BCL6-, BCL1-, cMYC-; R-IPI 4, CNS-IPI 4, Stage IV]. Chemotherapy with R-CHOP for four cycles resulted in a mixed response. Upon subsequent hospitalization, a second right inguinal lymph node biopsy was consistent with refractory DLBCL [positive for CD79a, CD20 (weak), MUM1, BCL2, BCL6, MIB1 Ki67 60-70% proliferative fraction, CD30 (1-2%), negative for CD10, CD3, CD5, BCL1, MYC]. Radiation followed by RICE given as second line therapy had no meaningful response on imaging. However, monoclonal protein resolved after a second cycle of RICE. Pathology indicated a CD19+ specimen on review. Polatuzumab vedotin was given as bridging therapy, followed by lymphodepletion regimen and ultimately CD19-targeted CAR T cell infusion. A partial response for lymphoma was seen at 90-day evaluation (Deauville 3). Immunofixation was positive as late as 16 days post infusion with no abnormality detected at subsequent testing 32 days post infusion. At three months, the M protei