FDA’s ODAC Casts Votes on the Use of Certain Treatment Options in Cancer Care

The United States Food and Drug Administration's (FDA) Oncologic Drugs Advisory Committee (ODAC) has casted their votes on the utilization of certain treatments in both the relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and multiple myeloma patient populations, respectively, according to information shared from the ODAC during a regulatory meeting.

The ODAC serves as an expert panel which reviews clinical data related to the safety and efficacy of both approved and investigational drug products intended for cancer treatment, according to the official United States FDA website, www.fda.gov. Based on its evaluations, the committee provides recommendations to the Commissioner of the United States FDA to help inform regulatory decisions.

The committee comprises 13 voting members, the website continues. These individuals are selected for their expertise in relevant fields such as general oncology, pediatric oncology, hematologic oncology, immunologic oncology, biostatistics and other related disciplines. Additionally, the committee may include a non-voting member who represents the pharmaceutical industry, contributing an industry perspective to the discussion without participating in voting.

For patients with high-risk smoldering multiple myeloma, the committee voted six to two in favor of the risk/benefit profile of subcutaneous (under the skin) Darzalex Faspro (daratumumab and hyaluronidase-fihj) as a monotherapy. This outcome was based on data from the phase 3 AQUILA trial.

For patients with relapsed/refractory DLBCL, the committee voted eight to one against applicability of Columvi (glofitamab-gxbm) plus gemcitabine and oxaliplatin in the United States patient population. This outcome was based on data from the phase 3 STARGLO study.

Here is what you need to know about each regulatory decision from the FDA's ODAC.

ODAC's Vote on the Risk/Benefit Profile of Subcutaneous Darzalex Faspro in Myeloma

With the FDA committee voting six to two in favor of the Darzalex Faspro risk/benefit profile for those with high-risk smoldering myeloma, this may present with a potential new option for people with this disease which is important because there are currently no FDA-approved treatments for the disease. Notably, smoldering multiple myeloma is an early sign that an individual may develop myeloma, a rare blood cancer, according to the Cleveland Clinic website.

The AQUILA study compared subcutaneous Darzalex Faspro with active monitoring for patients with the disease. In those patients who were treated with Darzalex Faspro, the time until disease progression was not yet reached compared with a progression-free survival of 41.5 months for those who were actively monitored. Moreover, the median overall survival was not reached in either treatment group, and the difference in five-year overall survival rates between the two arms was 6%.

Although there were higher rates of toxicities in the Darzalex Faspro treatment group, these infections were typically not severe and were short lived. In the Darzalex Faspro treatment group, more patients experienced any-grade treatment-emergent side effects (97 versus 84 patients), grade 3 (severe) and 4 (life-threatening) treatment-emergent side effects (40 versus 30 patients), serious side effects (29 versus 19 patients), treatment-emergent side effects leading to trial discontinuation (6 versus 0 patients) and leading to trial discontinuation leading to dose modifications (47 versus 0 patients) compared with those who were actively monitored.

“I consider myself lucky to be receiving treatment at an early stage of the disease process. More research should be done to optimize the timing of treatment for people with this condition. Nonetheless, I firmly believe it is worthwhile to provide people with a SOC treatment option, such as daratumumab monotherapy, that they could choose based on personal and medical factors,” Jeffrey Rubin, a patient with high-risk smoldering multiple myeloma, said during the meeting.

It is important to note that this treatment option has not yet been granted regulatory approval by the United States FDA for patients with high-risk smoldering multiple myeloma.

ODAC's Vote on Columvi and Chemo for Patients in the United States With Relapsed/Refractory DLBCL

Contrarily, on the same day, the FDA's ODAC also voted eight to one against the applicability of the STARGLO trial results in the United States relapsed/refractory DLBCL patient population. This is because most patients enrolled in the trial were from Asia, with only 9% being from North America, generating doubts that the trial results would be generalizable to the United States population

STARGLO evaluated Columvi plus chemotherapy and compared that with Rituxan (rituximab) plus chemotherapy in patients with relapsed/refractory DLBCL ineligible for autologous stem cell transplant. The primary end point of the study was overall survival, and the data showed that the Columvi combination improved the median overall survival versus the Rituxan combination in the overall combination, with a median overall survival of 25.5 months versus 12.9 months, respectively.

Despite these seemingly positive outcomes, there were regional subgroup inconsistencies, where were cited as a critical issue. In non-Asian patients, there was limited to no survival benefit observed, and in the United States patient subgroup specifically, the hazard ratio favored the Rituxan treatment. However, due to the small patient sample size, this limited interpretation.

During the meeting, Dr. Nicole Sunseri of the Division of Hematologic Malignancies in the Office of Oncologic Diseases at the FDA, said, “The treatment effect across all efficacy end points was inconsistent between the Asian and non-Asian regional subgroups. Given the size of the Asian subgroup and the magnitude of the treatment effect, it is likely that the overall study results are being driven by the Asian regional subgroup.”

The United States FDA previously granted accelerated approval to Columvi for the treatment of adult patients with relapsed/refractory DLBCL not otherwise specified in June 2023. This patient population also included patients with large B-cell lymphoma arising from follicular lymphoma following a minimum of two lines of treatment.

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