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Now that chimeric antigen receptor T-cell therapies have received FDA approval for diffuse large B-cell lymphoma (DLBCL) after moving quickly through early phase clinical trials, research is now exploring ways to shift these agents earlier in the treatment paradigm, according to a discussion at the 2nd Annual Live Medical Crossfire on Hematologic Malignancies.
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Andre Goy, MD, chief, Division of Lymphoma, chairman and director, John Theurer Cancer Center, discusses the progress made with immunotherapy for the treatment of hematologic malignancies over the last 5 years.

The biggest clinical unmet need in the treatment of patients with mantle cell lymphoma is overcoming resistance to BTK inhibitors, as patients who progress on treatment with ibrutinib (Imbruvica) and acalabrutinib (Calquence) are often incurable, according to Michael Wang, MD. Investigators are now challenged to find a new avenue of treatment.

Pembrolizumab (Keytruda) has been granted an accelerated approval by the FDA for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or those who have relapsed after 2 or more prior lines of therapy. The approval is based on results from 53 patients with relapsed/refractory PMBCL enrolled in the multicenter, open-label, single-arm KEYNOTE‑170 trial.

An objective response rate was achieved in 18 of 37 patients with relapsed/refractory non-Hodgkin lymphoma who received the combination of the BTK inhibitor ibrutinib with the PI3K inhibitor buparlisib, according to findings of a phase I/II trial reported at the 2018 ASCO Annual Meeting.

Durable complete remissions were seen in 46% of patients with high-risk diffuse large B-cell lymphoma treated with the CAR T-cell therapy lisocabtagene maraleucel at 6 months. These results come from the updated findings from the phase I, multicenter TRANSCEND trial that were presented at the 2018 ASCO Annual Meeting.

Based on data reported at the 2018 ASCO Annual Meeting, the primary endpoint of the phase III RELEVANCE trial was not met with the combination of rituximab plus lenalidomide showing similar efficacy results compared with rituximab plus chemotherapy in treatment-naive patients with follicular lymphoma. The chemotherapy-free regimen, however, did show a more favorable toxicity profile.

According to initial results from a phase Ib/II study presented at the 2018 ASCO Annual Meeting, 50% of a small group of patients with relapsed or refractory non-Hodgkin lymphoma achieved responses from the combination of an anti-CD47 antibody plus rituximab.

In an interview with <em>Targeted Oncology, </em>Andrew M. Evens, DO, MSc, discusses the clinical trials that are ongoing at Rutgers for patients with mantle cell lymphoma. He shares some details of the current treatment landscape and how that will evolve as more data becomes available from trials like those at his institution.

Expression of genes from the B-cell receptor pathway predicted shorter progression-free survival and overall survival in patients with mantle cell lymphoma, according to results from an examination of a subsection of patients in the ongoing Fondazione Italiana Linfomi MCL-0208 clinical trial.

Palbociclib, a CDK4/6 inhibitor, has demonstrated success against ibrutinib resistance in primary human samples and mantle cell lymphoma cell lines with the mutated BTKC481S protein. Its use has sparked an investigation of combination therapies targeting CDK4 in MCL, said Selina Chen-Kiang, PhD.

Brian T. Hill, MD, PhD, director of Lymphoid Malignancies at the Cleveland Clinic, discusses current combinations being investigated for the treatment of patients with mantle cell lymphoma.

Based on data from the phase II JULIET study, tisagenlecleucel has received FDA approval for the treatment of adult patients with relapsed/refractory large B-cell lymphoma—including diffuse large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma—after 2 or more lines of systemic therapy.

The FDA approved several indications throughout the month of April 2018. A number of drugs were granted priority review and Fast Track designation. The FDA also halted all clinical trials using tazemetostat as treatment, and new initiatives were introduced to help ease the development of genetic and genomic-based tests. Check out our list of all FDA happenings from April 2018.






While relapsed/refractory mantle cell lymphoma (MCL) is considered an aggressive disease, new findings show patients may benefit from adding chimeric antigen receptor T-cell therapy to their treatment regimen. ZUMA-2, a currently ongoing trial, aims to understand the potential benefits with axicabtagene ciloleucel, an anti-CD19 CAR T-cell product, for patients with relapsed/refractory MCL.

Enrollment has been halted by the FDA on clinical trials of tazemetostat in patients with various solid tumors and hematologic malignancies, according to Epizyme, the manufacturer of the EZH2 inhibitor.

Selina Chen-Kiang, PhD, a professor of pathology and immunology at Weill Cornell Medical College, discusses the rationale of her phase I trial investigating the use of CDK4/6 inhibitors for the treatment of patients with mantle cell lymphoma.

The B-Cell Lymphoma Moon Shot Program at The University of Texas MD Anderson Cancer Center wants to increase the cure rate of the disease from 30% to 60% within 5 years. In a presentation at the <em>22nd Annual</em> International Congress on Hematologic Malignancies, Michael Wang, MD, detailed results from 3 clinical trials that may help make that 5-year goal into a reality for patients with mantle cell lymphoma.

A novel bromodomain and extra terminal protein inhibitor demonstrated promising early activity and a manageable safety profile in the treatment of patients with relapsed or refractory lymphoma in the results of a first-in-human phase I trial.

Owen O’Connor, MD, PhD, director of the Center for Lymphoid Malignancies at New York-Presbyterian Hospital, discusses the possibility of using chimeric antigen receptor (CAR) T-cell therapies for the treatment of patients with mantle cell lymphoma (MCL). This can be tricky for a number of reasons, but O’Connor is hopeful that there are treatment regimens for this patient population that can work.

The field of mantle cell lymphoma underwent a significant change with the FDA approval of ibrutinib in 2013. Now, the recent approval of acalabrutinib has similarly impacted the treatment landscape, as experts say it could be associated with slightly fewer adverse events than ibrutinib, according to Andre Goy, MD.















































