There’s a lot happening in clinical practice with immunotherapy treatments: expanded indications for nivolumab and ipilimumab, biomarkers to judge patient response to combinations, and developments with CAR-T.
There’s a lot happening in clinical practice with immunotherapy treatments. Following are a few notable highlights:
1. Nivolumab in colorectal cancer
Although the programmed death-1 (PD-1) inhibitor nivolumab (Opdivo from Bristol-Myers Squibb [BMS]) has significantly trailed behind its competitor, pembrolizumab (Keytruda from Merck)—especially after nivolumab failed to improve outcomes as first-line treatment for patients with non—small cell lung cancer—the drug is being evaluated in a range of different tumor types, and as combination therapy.
A recent success for nivolumab is its accelerated approval as treatment of pediatric and adult patients with microsatellite instability—high (MSI-H) or mismatch repair–deficient metastatic colorectal cancer who have failed or are intolerant to prior treatment.
The CheckMate-142 trial, being conducted across 31 sites in 8 countries, noted an objective response rate of 28% in patients who had received a prior treatment with a fluoropyrimidine, oxaliplatin, or irinotecan. Thirty-two percent of the overall population responded to treatment, which included a 30% partial response.
2. Pediatric indication for ipilimumab
An early entrant in clinical practice, the cytotoxic T-lymphocyte associated protein 4 inhibitor ipilimumab (Yervoy from BMS) was the first checkpoint-inhibitor immuno-oncology agent to be approved for metastatic melanoma, back in 2011. Now, the indication has been expanded to include pediatric patients, 12 years and older, with unresectable or metastatic melanoma.
Yervoy was evaluated in 2 trials—a dose-finding study with 33 patients between the ages of 2 and 21 years old with relapsed or refractory solid tumors, and an open-label, single-arm trial in 12 patients between the ages of 12 and 16 years old with previously treated or untreated, unresectable stage 3 or 5 malignant melanoma—and demonstrated equivalent safety to the use of Yervoy in adults.
3. Ensuring patient response to combination immunotherapy in melanoma
With clinical trials evaluating several different combinations of immunotherapy agents, can we use predictive biomarkers as an early sign of patient response? A study recently published in the Journal of Clinical Investigation Insight attempted just that. The authors tried to correlate partially exhausted cytotoxic lymphocytes (peCTLs) and regulatory T lymphocyte levels in response to combination immunotherapy in 112 different melanoma tumors. The tumor samples were from patients who had received a PD-1 monotherapy or combination therapy.
Patients with low peCTL who were given combination therapy showed higher overall response rates (ORR) than patients who received the monotherapy, while in patients with high peCTL, ORR to anti-PD-1 monotherapy and combination therapy were similar. The authors concluded that fewer tumor-infiltrating peCTLs may be necessary to achieve a response to combination immunotherapy.
4. CAR-T cell progress in DLBCL
Kite Pharma’s anti-CD19 chimeric antigen receptor-T (CAR-T) cell treatment has resulted in remission for up to 56 months in patients with diffuse large B-cell lymphoma (DLBCL). The results from a long-term study in 7 evaluable patients with relapsed DLBCL who received the anti-CD19 CAR-T cells were published in Molecular Therapy. Of these patients, 5 demonstrated complete remission (CR), and in 4 these remissions were durable long-term—56, 51, 44, and 38 months, and none had relapsed.
These study results are encouraging news for this potentially revolutionary treatment, which has seen some setbacks in recent times. Juno Therapeutics had to halt its ROCKET trial that was evaluating JCAR015 in patients with acute lymphoblastic leukemia due to treatment-associated deaths.
5. ODAC approval for CAR-T
A giant step forward in the field of immunotherapy was the recent FDA Oncologic Drugs Advisory Committee (ODAC)'s unanimous recommendation of Novartis’ CAR-T treatment, CTL019, for children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia. The committee reviewed results from the phase 2 ELIANA study, which found 82% of patients reached CR or CR with incomplete blood count recovery at 3 months following CTL019 treatment.
Of course, neurological toxicity and cytokine release syndrome being a big concern with CAR-Ts, Novartis has developed a Risk Evaluation and Mitigation Strategy, which includes ways to communicate treatment-associated risks to providers and patients.
The final decision on CTL019 is expected in October.