Approval of New & Updated Indications for Temozolomide
The Food and Drug Administration (FDA) approved updated labeling for temozolomide under Project Renewal, an Oncology Center of Excellence initiative aimed at updating labeling information for older oncology drugs to ensure information is clinically meaningful and scientifically up-to-date. This is the second drug to receive a labeling update under this pilot program. The first drug that received approval under Project Renewal was capecitabine.
Project Renewal is a collaborative program that leverages external oncology experts and early-career scientists to review existing published literature and gain first-hand experience in the selection, curation, and evaluation of evidence for independent FDA review. Project Renewal is intended to keep older, commonly prescribed oncology drugs' labeling up-to-date, while providing transparency on FDA's evaluation process and evidentiary standards, and improving awareness of drug labeling as an information resource.
Temozolomide is now approved for the following new and revised indications:
* adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma; and
* treatment of adults with refractory anaplastic astrocytoma.
Additional labeling revisions include the following:
* The dosage regimen is revised and updated for newly diagnosed glioblastoma and refractory anaplastic astrocytoma.
* For temozolomide capsules, information on risks from exposure to opened capsules is added under Warnings and Precautions.
* Patient Counseling Information section and the Patient Information document are updated and revised.
One approved indication for temozolomide remains the same: treatment of adults with newly diagnosed glioblastoma, concomitantly with radiotherapy and then as maintenance treatment.
Project Renewal is limited to updating labeling of older oncology drugs with decades of use, multiple supportive clinical studies, and substantial post-marketing experience. For information on the key studies supporting a new or revised indication, see temozolomide prescribing information.
Motixafortide + Filgrastim for Mobilization of Hematopoietic Stem Cells for Multiple Myeloma
The FDA has approved motixafortide in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma. Motixafortide is administered by injection for subcutaneous use.
Autologous stem cell transplantation (ASCT) is part of the standard of care treatment paradigm for multiple myeloma and delivers prolonged survival for patients with this cancer type. The success of ASCT depends on adequate mobilization of stem cells during the treatment process. The American Society for Transplantation and Cellular Therapy guidelines recommend a collection target of 3-5 x 106 CD34+ cells/kg. Additionally, collection of a sufficient number of stem cells to perform two transplantations is recommended. Historically, depending on induction regimens and mobilization strategies, up to 47 percent of patients have had challenges collecting target numbers of hematopoietic stem cells for ASCT after one apheresis session.
"Greater numbers of patients with multiple myeloma are candidates for autologous stem cell therapy; however, achieving target collection goals can be difficult in some patients given modern barriers, including the treatment of older patients and use of contemporary induction regimens," said John DiPersio, MD, PhD, primary investigator for the GENESIS trial and Professor of Medicine, Pathology, and Immunology and Director of the Center for Gene and Cellular Immunotherapy at Washington University School of Medicine in St. Louis. "Innovation in this area of medicine has been needed, and today's approval of motixafortide addresses the demand for new therapies that can meet today's challenges by delivering more reliability in stem cell mobilization, versus filgrastim alone, with fewer days of apheresis sessions and fewer doses of filgrastim for people living with this cancer."
The FDA approval of motixafortide is based on results from the two-part, Phase III GENESIS trial, a randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of motixafortide plus filgrastim, compared to placebo plus filgrastim, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Part 1 was a single-center, lead-in, open-label study involving 12 patients treated with motixafortide plus filgrastim designed to ascertain the dose. Part 2 involved 122 patients who were randomized 2:1 in a double-blind, placebo-controlled, multicenter study.
The assessment of CD34+ cells was performed by central and local laboratories. Central laboratory assessments were used for the efficacy results. Local laboratory results were used for clinical treatment decisions. Motixafortide plus filgrastim enabled 67.5 percent of patients to achieve the stem cell collection goal of >=6 x 106 CD34+ cells/kg within two apheresis sessions versus 9.5 percent for the placebo plus filgrastim regimen, as measured by central laboratory. Additionally, 92.5 percent of patients reached the stem cell collection goal in up to two apheresis sessions in the motixafortide arm and 21.4 percent in the placebo arm, as measured by local laboratories. Local laboratory data were used for a sensitivity analysis. The data are descriptive and were not statistically powered nor prespecified. Therefore, the information should be cautiously interpreted.
In GENESIS, the safety was evaluated in 92 patients with multiple myeloma who received motixafortide 1.25 mg/kg subcutaneously plus filgrastim, and 42 patients who received placebo plus filgrastim. Serious adverse reactions occurred in 5.4 percent of patients receiving motixafortide plus filgrastim. These reactions included vomiting, injection site reaction, hypersensitivity reaction, injection site cellulitis, hypokalemia, and hypoxia. The most common adverse reactions occurring in GENESIS (incidence >20%) were injection site reactions (pain, erythema, and pruritus), flushing, and back pain.
Increased age, as well as exposure to lenalidomide-containing induction regimens, including 3-4 drug combination regimens, have been associated with impaired stem cell mobilization. The GENESIS study included patients considered representative of the typical multiple myeloma population undergoing ASCT, with a median age of 63 years and with ~70 percent of patients in both arms of the trial receiving lenalidomide-containing induction therapy. In this contemporary population, patients in the motixafortide plus filgrastim arm were able to mobilize more than 4 times the amount of stem cells with a single dose over a 24-hour period compared with placebo plus filgrastim.