Diffuse large B cell lymphoma (DLBCL), the most common type of Non‐Hodgkin lymphoma (NHL), comprises a heterogeneous group of diseases with different biology, clinical presentations, and response to treatment. R‐CHOP remains the mainstay of therapy and can achieve long‐term disease control in nearly 90% of patients presenting with limited‐stage and in up to 60% of those presenting with advanced stages. Advances on the understanding of the genetic landscape and molecular features of DLBCL have identified high‐risk subsets with poor outcomes to chemo‐immunotherapy that are actively being studied in clinical trials. Novel therapies could potentially improve outcomes for patients with high‐risk disease. Studies evaluating risk‐adapted therapy based on classification by cell of origin (COO) and molecular features are ongoing. Developments in the fields of immunotherapy, mostly with adoptive T‐cell therapy, have significantly improved the outcomes of patients with relapsed refractory disease. In this review, we will summarize the recent data and discuss ongoing efforts to improve DLBCL treatment in the frontline and relapsed refractory settings.

Multiple myeloma (MM) is a malignant plasma cell disorder that remains incurable for most patients despite significant improvements achieved with modern therapy. Tumor evasion is a key process in the pathogenesis of MM and a compromised immune system is associated with more aggressive forms of the disease. In contrast, the emergence of myeloma‐specific immune responses after both autologous and allogeneic stem cell transplantation is associated with better prognosis. Adoptive T cell therapies may improve specific anti‐myeloma immunity resulting in long‐lasting remissions. CAR T cell therapies for MM are at an early stage of clinical development. To date, anti‐BCMA CAR T cells have shown the greatest results in early‐phase clinical trials. Toxicities have included cytokine release syndrome (CRS) and neurotoxicity. Current areas of research in CAR T cell therapies include the use of gene‐editing to enhance their effectiveness and safety, the integration of CAR T cells with other therapies (immunomodulatory drugs, checkpoint inhibitors) and CAR T cells to target multiple antigens.

We conducted a phase 1 clinical trial of anti-BCMA CAR T cells (CART-BCMA) with or without anti-CD19 CAR T cells (huCART19) in multiple myeloma (MM) patients responding to third- or later- line therapy (Phase A, N=10) or high-risk patients responding to first-line therapy (Phase B, N=20), followed by early lenalidomide or pomalidomide maintenance. We observed no high-grade CRS and only one instance of low-grade neurologic toxicity. Among 15 subjects with measurable disease, 10 exhibited PR or better; among 26 subjects responding to prior therapy, 9 improved their response category and 4 converted to MRD-negative CR/sCR. Early maintenance therapy was safe, feasible, and coincided in some patients with CAR T cell re-expansion and late-onset, durable clinical response. Outcomes with CART-BCMA + huCART19 were similar to CART-BCMA alone. Collectively, our results demonstrate favorable safety, pharmacokinetics, and antimyeloma activity of dual-target CAR T cell therapy in early lines of multiple myeloma treatment.

Background Autologous stem cell transplantation (ASCT) is a commonly used treatment for multiple myeloma (MM). This retrospective cohort study characterizes the risk factors and outcomes associated with bacteremia following ASCT at a single center. Methods We conducted a retrospective analysis in subjects who underwent ASCT for multiple myeloma and other malignancies from May 2014 to March 2015 at a single center. The control cohort included all subjects undergoing ASCT in the same time period who did not develop bacteremia. Results During the study period, 363 ASCTs were completed in 282 discrete patients. Bacteremia was documented in 13% of all transplants. Enterococcus faecium was the most frequent species overall (14/62, 23%). Vancomycin resistance was present in 93% of E faecium isolates. Bacteremia was associated with a significantly decreased survival in patients who received their transplant after the first year of myeloma treatment. Overall survival (OS) was not significantly different in the two cohorts among patients undergoing ASCT within the first year of myeloma treatment. Survival analysis showed a significantly decreased OS in patients who developed Enterococcus bacteremia as compared to the non‐bacteremia cohort. Enterococcal bacteremia was associated with significantly longer duration of neutropenia (mean 14 vs 9.7 days, P = 0.01), hospitalization (mean 61.7 vs 20.4 days, P = 0.0006), and higher mortality (69% vs 25%, P = 0.01) as compared to other bacteremias. Conclusion We found a high incidence of E faecium and a low incidence of MRSA and Pseudomonas bacteremias following ASCT in our patient population. Survival analysis in our cohort suggests that the effect of underlying disease status and cumulative chemotherapy is critically important in determining outcomes related to bacteremia. Enterococcal bacteremias following ASCT were associated with significantly higher morbidity and mortality than non‐enterococcal bacteremias.

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