FDA Approves Subcutaneous Administration of Rituximab for Three Lymphoma Types

On June 22, 2017, the United States Food and Drug Administration (FDA) approved subcutaneous injection of rituximab plus hyaluronidase human for people with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL). Subcutaneous administration refers to the method of delivering a drug under the skin rather than directly into a vein as performed during intravenous (IV) administration.

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Administration of rituximab under the skin tends to take less than 10 minutes, whereas the traditional IV method can last several hours. The technique also allows for fixed dosing, which can reduce preparation time and excess drug waste, and may be more cost effective than IV infusion.

The approved treatment is to be employed only after patients have received at least one cycle of intravenous rituximab.

Approval comes based on the results of a series of clinical trials demonstrating comparable safety and efficacy outcomes across subcutaneous and intravenous administration.

New Immunotherapy Treatment Approved for Children and Adults with Hodgkin Lymphoma

On March 14, 2017, the Food and Drug Administration (FDA) approved pembrolizumab for the treatment of refractory Hodgkin lymphoma in children and adults who have been treated with at least three prior therapies.

Pembrolizumab is a type of immunotherapy called a checkpoint inhibitor. This drug consists of an antibody that binds to programmed death receptor-1 (PD-1), preventing the cancer cells from evading detection by the body’s immune system. Treatment with pembrolizumab allows T-cells (the fighter cells) to mount an immune response against the malignant cells.

Since 2014, Pembrolizumab has been FDA approved for the treatment of unresectable or metastatic melanoma, metastatic non-small-cell lung cancer, and recurrent or metastatic head and neck squamous cell carcinoma. The approval of pembrolizumab for the treatment of relapsed Hodgkin lymphoma was made under the FDA’s accelerated approval process.

This approval was based on data from a clinical trial of pembrolizumab in 210 adult patients with Hodgkin lymphoma who had relapsed or refractory disease after autologous stem cell transplant and/or treatment with brentuximab vedotin.  With a median follow up of 9.4 months, the overall response rate was 69%, including partial responses in 47% and complete responses in 22% of patients. The approval in pediatrics was based on known safety data and extrapolated efficacy based on the adult trial.

The most common adverse events in the trial were fatigue, fever, cough, musculoskeletal pain, diarrhea, and rash. Among 40 pediatric patients with advanced melanoma, PD-L1 positive tumors, or lymphoma, the side effects and overall safety profile was similar to adults.  A “warning and precaution” was added to the label describing the potential complications of graft-versus-host disease (GVHD) in patients undergoing allogeneic stem cell transplant after treatment with pembrolizumab.  Death related to GVHD has occurred and physicians are advised to monitor for hepatic veno-occlusive disease and grade 3-4 acute GVHD including hyperacute GVHD.

The recommended dose of pembrolizumab for patients with Hodgkin lymphoma is 200mg every 3 weeks in adults and 2mg/kg (up to 200mg) every 3 weeks in children.

At the Weill Cornell and NewYork-Presbyterian Lymphoma Program, we offer pembrolizumab as one of many treatment choices available for people with Hodgkin lymphoma.

FDA Approves First-Ever Targeted Marginal Zone Lymphoma Treatment

On January 19, 2017, the United States Food and Drug Administration (FDA) approved ibrutinib to treat patients that have received at least one line of prior therapy for marginal zone lymphoma (MZL), a type of non-Hodgkin lymphoma (NHL).

MZL is an indolent B-cell lymphoma that accounts for 5-10% of all lymphomas and lacks a standard of care. Current MZL treatments include anti-CD-20 antibody therapy (e.g. rituximab) or chemotherapy. However, ibrutinib is the first-ever treatment to specifically be approved for MZL.

Ibrutinib works by inhibiting Bruton’s tyrosine kinase (BTK), an enzyme responsible for transmitting pro-growth and survival signals from the surface of a cell to its nucleus. In this way, ibrutinib may interfere with chronic stimulation arising from inflammation in the tumor microenvironment; thus slowing the growth of B-cells.

The Weill Cornell Lymphoma Program is proud to have played a role in the phase 2 trial — the largest trial to date for people with previously treated MZL of all subtypes —leading to FDA approval for ibrutinib. Roughly half of all patients had a significant response to ibrutinib, with some degree of tumor shrinkage observed in almost 80% of all patients in the trial. Roughly one-third remained on treatment 18 months after beginning treatment.

The most common side effects included fatigue, diarrhea, and anemia. These side effects were manageable, and consistent with previous research, although some cases required the discontinuation of treatment with ibrutinib.

Results from this study support the use of ibrutinib as an effective well tolerated chemotherapy-free option for the treatment of previously treated MZL. However, some questions remain. MZL is a heterogeneous group of lymphomas, and it is unclear which subtypes might respond best to ibrutinib. With only half of all previously treated MZL patients responding to ibrutinib, improvements might be realized by combining ibrutinib with other drugs and/or using it earlier in the treatment of MZL.

At Weill Cornell, we are currently studying ibrutinib in combination with the immunotherapy drug durvalumab in people with previously treated indolent non-Hodgkin lymphoma, including MZL.