Breyanzi Receives Extended FDA Approval
On June 24, 2022, the indication for Bristol Myers Squibb’s chimeric antigen receptor (CAR) T cell therapy, Breyanzi® (lisocabtagene maraleucel) suspension was expanded by the U.S. Food and Drug Administration (FDA).
In addition to its original approval as third-line or later therapy for treating adults who have certain subtypes of diffuse large B-cell lymphoma (DLBCL), it now is indicated as second-line use in the same cancers. Included are patients who have not responded to or who have relapsed within one year of treatment with chemotherapy and immunotherapy (chemoimmunotherapy) for DLBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma and follicular lymphoma (FL) grade 3B.
Its use may be appropriate for some patients who are not candidates for stem cell transplants, as well. In the TRANSFORM clinical trial that led to the new approval, event-free survival (EFS) for patients receiving Breyanzi averaged 10.1 months as compared with 2.3 months for patients using the standard of care. Two-thirds of the participants who got Breyanzi achieved complete remissions (CR) versus about two-fifths of the group that got usual care. B-cell lymphomas produce CD19 proteins on their cell surfaces. Breyanzi is produced by collecting and then altering some of the patient’s T cells so that they bind specifically to CD19. When the modified CAR-T cells are infused back into the patient, they inactivate CD19, destroying the cancer cells that produce it. Because using it may be associated with potentially fatal neurological side effects and cytokine release syndrome (CRS),
Breyanzi has both boxed warnings and a risk evaluation and mitigation strategy (REMS). Neurological problems may include confusion, headaches, seizures and tremors. CRS is a flu-like reaction that can result in cardiac arrest.
Given only in healthcare facilities certified to administer it, Breyanzi can be given as either inpatient or outpatient regimens. Staff members receive specialized training to treat patients who get it and to recognize and manage potential side effects.
Pediatric Indication for Qsymia
The FDA broadened the indication for Qsymia® (phentermine/topiramate – Vivus) extended-release capsules on June 24, 2022. Now indicated for children as young as 12 years old, it is add-on treatment with diet changes and exercise to provide management of chronic overweight and obesity.
To be eligible, patients who are between 12 years and 18 years old need to be in the upper 5% of body mass index (BMI) compared to their same age and gender peers. They must be unable to lose weight through dieting and exercise alone. In a placebo-controlled clinical study, adolescents taking Qsymia lost an average of up to 7.1% of their BMI as opposed to an average 3.3% gain for those taking placebos. The recommended dose is one 3.75mg phentermine/23mg topiramate capsule each morning for two weeks, increased to one 7.5mg phentermine/46mg topiramate capsule every morning.
Therapy should be assessed every three months for dose adjustments, if needed. When ending treatment, Qsymia should be tapered off and not stopped abruptly. It also is approved for adults whose BMI is at least 30 kg/m2 or whose BMI is 27 kg/m2 or higher and who have at least one weight-related condition such as high blood pressure, type 2 diabetes or high cholesterol.
A REMS warns prescribers and patients about the risk of birth defects that is associated with taking Qsymia. Female patients of child-bearing age must also use an effective form of contraception and test for pregnancy on a monthly basis, beginning before treatment starts. Because some patients have experienced metabolic acidosis while taking Qsymia, blood chemistry profiles of each patient also should be checked before beginning treatment and periodically during therapy.
MedWatch Update: Copiktra
The FDA issued a safety communication for Copiktra® (duvelisib) capsules on June 30, 2022. In a required post-marketing continuation of a clinical study, the chance of dying or suffering serious side effects may have been higher for patients taking Copiktra to treat chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) than for patients using a different drug.
Copiktra is an oral phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma inhibitor that blocks the spread of cancer cells. It has boxed warnings that 31% of patients in clinical trials had severe infections, including sepsis, while taking it, and that 18% of trial participants developed serious diarrhea and/or colitis. Smaller percentages of study patients experienced dangerous skin reactions or pneumonitis. Side effects caused death for some of the patients.
The FDA is encouraging prescribers to discuss the advantages and risks of taking Copiktra with their patients. For those who keep taking it, blood counts and liver function should be checked frequently.