FDA Approval Summary: Lisocabtagene Maraleucel for Second-Line Treatment of Large B-Cell Lymphoma.

In June 2022, the FDA extended the indication for lisocabtagene maraleucel (liso-cel) to include adults with large B-cell lymphoma (LBCL) who have refractory disease or relapse within 12 months of first-line chemoimmunotherapy (CIT), as well as transplant-ineligible adults with refractory disease or relapse after first-line CIT. Two clinical trials evaluating a single infusion of liso-cel preceded by lymphodepleting chemotherapy supported the second-line indications. TRANSFORM is a randomized, phase 3, open-label trial comparing liso-cel with standard second-line therapy, including planned autologous hematopoietic stem cell transplantation (HSCT), in 184 transplant-eligible patients.

FDA Approval Summary: Axicabtagene Ciloleucel for Second-Line Treatment of Large B-Cell Lymphoma.

In April 2022, the FDA approved axicabtagene ciloleucel (axi-cel) for adults with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. Approval was based on ZUMA-7, a randomized (1:1), open-label trial in 359 patients with primary refractory LBCL (74%) or early relapse who were transplant candidates. The study compared a single course of axi-cel to standard therapy, consisting of chemoimmunotherapy followed by high-dose therapy and autologous hematopoietic stem cell transplantation (HSCT) in responding patients.

FDA Approval Summary: Brexucabtagene Autoleucel for Treatment of Adults With Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia.

In October 2021, the FDA approved brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL). Approval was based on the phase II portion of ZUMA-3, a single-arm, open-label, multicenter trial that evaluated a single infusion of brexu-cel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine, in this population. Efficacy was established on the basis of complete remission (CR) within 3 months after infusion and the duration of CR (DOCR).

FDA Approval Summary: Axicabtagene Ciloleucel for Relapsed or Refractory Follicular Lymphoma.

In March 2021, the U.S. Food and Drug Administration granted accelerated approval to axicabtagene ciloleucel, a CD19-directed chimeric antigen receptor T-cell therapy, for the treatment of adult patients with relapsed or refractory follicular lymphoma (r/r FL) after at least 2 lines of systemic therapy.

Clinical Development of Gene Therapies: The First Three Decades and Counting.

In the past three decades the field of gene therapy has made remarkable progress, surging from mere laboratory experiments to Food and Drug Administration (FDA)-approved products that bring significant reduction in disease burden to patients who previously had no therapeutic options for their serious conditions. Herein, we review the evolution of the gene therapy clinical research landscape and describe the gene therapy product development programs evaluated by the FDA in Investigational New Drug applications received in 1988-2019. We also discuss the clinical development programs of the first six oncolytic and gene therapy products approved in the United States.

Regenerative Medicine Therapies for Rare Diseases.

The field of regenerative medicine is growing rapidly with the introduction of new therapies that have the potential to treat and cure serious medical conditions, including rare diseases, for which there are no available treatments. In the United States, the development of novel medical products is regulated and guided by the Food and Drug Administration (FDA). As scientific and technological advances are discovered and adopted by the medical industrial enterprise, the FDA's implementation of policies that create a climate conducive to safe development and rapid availability of novel medical products is one of the pillars which support the Agency's mission of protecting and promoting the public health.

Central site monitoring: results from a test of accuracy in identifying trials and sites failing Food and Drug Administration inspection.

Background: Site monitoring and source document verification account for 15%-30% of clinical trial costs. An alternative is to streamline site monitoring to focus on correcting trial-specific risks identified by central data monitoring. This risk-based approach could preserve or even improve the quality of clinical trial data and human subject protection compared to site monitoring focused primarily on source document verification.

Oral allergy syndrome (pollen-food allergy syndrome).

A case of Oral Allergy syndrome or Pollen-Food Allergy Syndrome is briefly discussed. The clinical characteristics, diagnosis, pathogenesis, and management of this syndrome are discussed followed by clinical pearls and pitfalls for the practicing allergist. Symptoms generally occur with the ingestion of raw fruits/vegetables and nuts; cooked foods are not a problem.