Conference Casts a Wide Net to Reach the Whole Cancer Team

Ajai Chari, MD

Successfully treating and managing cancer takes a team effort, so having everyone on the same page is paramount. Each team member has their expertise to contribute to optimize patient outcomes. That is the distinguishing characteristic of the 40th Annual CFS® Innovative Therapy for Tomorrow®, a hybrid interactive conference taking place November 9-11, 2022, in New York, New York.

“CFS® [Chemotherapy Foundation Symposium] reaches a wide audience. It focuses on the community oncologist but also nurses, nurse practitioners, physician assistants, advanced practitioners, and also fellows,” Ajai Chari, MD, professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai, director of clinical research, Multiple Myeloma Program, associate director of clinical research at the Mount Sinai Health System in New York, New York, said in an interview with Targeted Therapies in Oncology™. “The progress of cancer is so rapid that you need presentations that provide overviews of treatment strategies that cover all disciplines.”

Chari is 1 of 3 cochairs for the conference, along with Benjamin Levy, MD, associate professor at Johns Hopkins School of Medicine in Washington, DC, clinical director of medical oncology at the Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, and Tiffany A. Traina, MD, an associate attending physician, vice chair of oncology in the Department of Medicine, and section head of the Triple Negative Breast Cancer Clinical Research Program at Memorial Sloan Kettering Cancer Center and an associate professor of medicine at Weill Cornell Medicine in New York, New York.

Another benefit of CFS® is the diversity of topics that cover many disciplines (AGENDA). In addition to hematology topics, specific presentations focusing on gynecologic, breast, dermatologic, lung, head and neck, and genitourinary cancers fill the 3-day conference. “Sometimes it’s nice to hear about advancements in other diseases than your own,” Chari said. “They say the biggest advancements in science and medicine are actually at the intersection of fields. It’s great to see what’s happening in other fields and think about how it might help you treat your patients.”

Chari noted that the conference limits presentations to 15 minutes each, which can be both a stick and a carrot. “In some ways, developing a 15-minute presentation is harder than developing a longer one,” Chari said. “As a presenter, it means you have to be very focused on the content, delivering the most impactful information.”

Multiple Myeloma Update

Turning to the latest developments, Chari said that multiple myeloma was generally considered a chronic disease until chimeric antigen receptor (CAR) T-cell therapy came on the scene. “The game changer about CAR T-cell therapy is that it’s one and done,” Chari said.

In March 2021, the FDA approved the first cellular therapy for patients with multiple myeloma, idecabtagene vicleucel (Abecma), for adult patients with relapsed or refractory disease after 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.¹ Findings from the phase 2 KarMMa trial (NCT03361748) revealed that 26% of treated patients achieved minimal residual disease–negative status and 79% of the patients who achieved a complete response or better were minimal residual disease–negative.²

The trial enrolled 140 patients who had received at least 3 prior treatment regimens for multiple myeloma, including an immunomodulatory drug a proteasome inhibitor, and an anti-CD38 antibody, and were refractory to their last treatment regimen. Patients received 1 of 3 doses of idecabtagene vicleucel (150 x 10⁶, 300 x 10⁶, or 450 x 10⁶ CAR-positive T cells) following lymphodepletion with fludarabine (30 mg/m2/day) and cyclophosphamide (300 mg/m2/day). Patients were followed for 24 months or more and then asked to participate in a long-term follow-up study (GC-LTFU-001; NCT03435796).

The second CAR T-cell therapy, ciltacabtagene autoleucel (Carvykti), was approved in February 2022 for the treatment of adult patients with relapsed or refractory multiple myeloma after 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.³

Safety and efficacy findings from the CARTITUDE-1 trial (NCT03548207) led to this agent’s approval.⁴

At a median follow-up of 18 months, overall results from the CARTITUDE-1 trial showed an objective response rate of 98%, with 80% of patients achieving a stringent complete response. Median duration of response in the overall population was 21.8 months (95% CI, 21.8-not estimable), with an 18-month progression-free survival and overall survival of 66% and 81%, respectively.⁴

Although the agents are commercially available, manufacturing limitations and cost of therapy remain a challenge. “There are next-generation CARs that can be made in less time and others that are expected to be available ‘off the shelf’ to avoid the long wait times,” Chari said.

Areas in which CAR T might be considered include for patients with early disease, newly diagnosed disease, or at first relapse. “In this setting, we don’t wait for patients to exhaust all therapies,” Chari said. Moving up CAR T-cell therapy earlier in the disease course, in less heavily treated patients whose immune system hasn’t been subjected to years of treatment and disease is a strategy that is being explored.

Bispecific antibodies are another novel immunotherapeutic modality, Chari noted. These agents have demonstrated a favorable safety profile and preliminary efficacy in heavily treated patients with multiple myeloma. Although more data are needed, bispecific antibodies will likely become part of the armamentarium for multiple myeloma in the future.

Unmet Needs

Chari summarized the current unmet needs in myeloma, focusing on multidrugrefractory disease, high-risk myeloma, extramedullary myeloma, myeloma in frail and older patients, central nervous system relapse, and patients with kidney disease that leads to renal failure. “These patients are often excluded from clinical trials,” Chari said.

A big challenge is that multiple myeloma is a very heterogeneous disease. Taking a 1-size-fits-all approach is not possible when the patient population is wide ranging. “A patient who is 50 years of age will tolerate treatment differently than a person who is 90 years of age, or even a patient who is 20 years old,” Chari said, adding that in older patients, if there is no response with the first or second treatment regimen, the outlook can be grim.

Chari said the findings from the MAIA trial (NCT02252172) hold promise.⁵ Investigators added daratumumab (Darzalex) to lenalidomide (Revlimid) plus dexamethasone and compared it to lenalidomide plus dexamethasone in newly diagnosed patients with multiple myeloma who were ineligible for autologous stem cell transplantation.

Investigators reported that the estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% CI, 65.0%-75.4%) in the daratumumab group and 55.6% (95% CI, 49.5%- 61.3%) in the control group (HR, 0.56; 95% CI, 0.43-0.73; P < .001).⁵

The percentage of patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group (P < .001). A total of 24.2% of patients in the daratumumab group vs 7.3% of patients in the control group had results below the threshold for minimal residual disease (1 tumor cell per 105 white cells) (P < .001).⁵

_REFERENCES:

_{1. FDA approves idecabtagene vicleucel for multiple myeloma. FDA. Updated March 29, 2021. Accessed June 27, 2022. https://bit.ly/3u5UQre}

_{2. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850}

_{3. FDA approves ciltacabtagene autoleucel for relapsed or refractory multiple myeloma. FDA. Accessed June 28, 2022. https://bit.ly/3Nu2CSH}

_{4. Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398(10297):314-324. doi:10.1016/S0140-6736(21)00933-8}

_{5. Facon T, Kumar S, Plesner T, et al; MAIA Trial Investigators. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104-2115. doi:10.1056/NEJMoa1817249}