Introduction: Ubiquitous expression of CD19 on B cell non-Hodgkin lymphoma identified it as a potential target for immune-based therapies.Areas covered: This article reviews the current literature on anti-CD19 therapies currently in clinical trials including monoclonal antibodies (mAb), antibody targeted cytotoxic drug conjugates (ADC), bispecific antibodies, and chimeric antigen receptor (CAR) modified T cells.Expert opinion: Naked anti-CD19 mAbs have shown little clinical benefit in B cell lymphomas. Despite unusual toxicity profiles with many anti-CD19 ADCs slowing development, durable remissions in a substantial minority of patients with refractory aggressive lymphomas should encourage continued efforts in this area. Blinatumomab, an anti-CD19 bispecific T cell engager, has shown impressive responses in relapse/refractory diffuse large B cell lymphoma (DLBCL), but is plagued by neurotoxicity issues and the need for continuous infusion. CD19 targeting CAR-T cell therapies are the most promising...

CD19-targeted immunotherapies for treatment of patients with non-Hodgkin B-cell lymphomas

Rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone immunochemotherapy remains standard of care for first-line treatment of diffuse large B-cell lymphoma (DLBCL). High-dose chemotherapy and stem cell transplantation is offered to most relapsing/refractory patients who respond to salvage therapy. This Q&A review evaluates recommended management strategies for second and subsequent lines of therapy in patients with DLBCL, outlining the relative efficacies of currently available options including novel agents such as ibrutinib and CAR-T cells. The combination of pixantrone and rituximab is currently under investigation as a second-line treatment for patients ineligible for stem cell transplantation, while pixantrone monotherapy is the only therapeutic option approved for multiply relapsed and refractory DLBCL beyond the second line at this time.

The rationale for combination therapy in patients with aggressive B-cell non-Hodgkin lymphoma: ten questions.

Since the introduction of anti-CD20 antibodies and polychemotherapy, diffuse large B‑cell lymphoma (DLBCL) has become a treatable, and, for a high proportion of patients, curable disease. However, a sizeable proportion of patients, especially in poor-prognosis subgroups, will relapse. The landscape of therapy in DLBCL has seen some exciting changes in the past years, most notably with the introduction of CAR-T-cell therapy. All three major trials were recently updated and showed sustained responses and excellent preliminary survival data. Other immunotherapies are gaining ground as well, as the antibody–drug conjugate polatuzumab vedotin has shown to be effective in relapsed DLBCL in combination with chemo-immunotherapy (rituximab and bendamustine). Complete remission rates increased from 15 to 40% and overall survival from 4.7 to 11.8 months. Polatuzumab is also being studied in previously untreated patients and results are awaited in 2019. Checkpoint inhibitors, the mainstay of therapy in a variety of malignancies, are also being studied in DLBCL. Interim results of an ongoing phase I/II study of atezolizumab with R‑CHOP in previously untreated patients show 83% complete remissions in early data. Other novel substances, like anti-CD47-antibodies and PI3-kinase inhibitors, show promising efficacy in early trials in relapsed patients as well.

Diffuse large B‑cell lymphoma

Aggressive B-cell non-Hodgkin lymphoma (aNHL) accounts for ∼50% of all NHL cases. The only potentially curative, broadly available treatment for patients with relapse, failing frontline treatment, is high-dose therapy followed by autologous stem cell transplantation (ASCT); patients ineligible for/who have failed ASCT have limited standard-of-care options. We conducted a structured review of treatments for relapsed/refractory patients with aNHL based on literature published between 2006 and 2017. Of the 22 publications identified for inclusion, most described phase II, single-arm trials (N = 25-217), and only three were randomized studies (phase II [N = 96], phase II/III [N = 111] and phase III [N = 338]). The majority of treatments evaluated resulted in only modest efficacy (median progression-free survival, 2.1-20.0 months) and ultimately poor health outcomes (median overall survival, 25 weeks-15.5 months). In conclusion, there is an unmet need for novel, effective, and tolerable treatments for patients with relapsed/refractory aNHL who are ineligible for/have failed ASCT.

Treatment of aggressive B-cell non-Hodgkin lymphoma beyond frontline therapy in patients not eligible for stem cell transplantation: a structured review.

7514Background: The Fc-enhanced CD19 antibody MOR208 and the immunomodulatory drug LEN have demonstrated single agent activity in patients (pts) with R-R DLBCL. MOR208 and LEN have shown synergy in...

L-MIND: MOR208 combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large B-cell lymphoma (R-R DLBCL) - a single-arm phase II study

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L-MIND: MOR208 combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large B-cell lymphoma (R-R DLBCL) - a single-arm phase II study