Dr Shah on Disease-Related Exacerbation With ICIs in Patients With Cancer and Preexisting NAIDs

"Although ICIs can be used safely [in this patient population], we still don't yet know [for] whom that is going to be the case. The likelihood of a relapse or severe worsening is relatively high [for patients with myasthenia gravis]. We have to be very careful when considering ICIs for these patients."

Shailee S. Shah, MD, a clinical assistant professor of Neurology (MS/Neuroimmunology) at Northwestern University Feinberg School of Medicine, shared findings from a retrospective cohort study assessing the exacerbation of pre-existing neurologic autoimmune disorders (NAIDs) in patients with cancer receiving immune checkpoint inhibitors (ICIs), as well as clinical outcomes with this therapy across conditions. 

The study included 135 patients with multiple sclerosis (n = 45), myasthenia gravis (n = 18), Guillain-Barré syndrome (n = 10), and Parkinson’s disease (n = 57), which served as the control cohort.

, and showed that NAID exacerbations were most frequently observed in patients with myasthenia gravis, with 67% experiencing a relapse, Shah reported. Among these patients, 50% required hospitalization and 17% died, indicating a high risk of severe adverse effects. In contrast, the exacerbation rate in patients with multiple sclerosis was 18%, and there were no significant differences in cancer response rate, progression-free survival, or overall survival across the NAID subgroups.

Although patients with myasthenia gravis receiving active immunosuppressive therapy appeared less likely to experience exacerbations, the sample size was insufficient to determine statistical significance, Shah explained. Among those with exacerbations, half required hospitalization and immunosuppressive treatment, and 56% subsequently discontinued ICI therapy, she said. One patient who was rechallenged with an ICI after initiating immunosuppressive therapy tolerated it well, Shah noted. However, 2 patients died due to complications related to worsening myasthenia gravis.

These findings highlight the importance of careful risk–benefit assessment when considering ICIs for patients with pre-existing NAIDs, particularly myasthenia gravis, Shah asserted. Although durable oncologic responses were observed in many patients who continued ICI therapy, the potential for severe neurologic exacerbation must be weighed when determining treatment appropriateness in this high-risk subgroup, she concluded.

Videos

Shailee S. Shah, MD, shares data on the frequency and severity of NAID exacerbation with ICIs in patients with cancer.

Dr Shah on Outcomes With Checkpoint Inhibition in Patients With Cancer and Pre-Existing Neurologic Autoimmune Disorders

Matthew H. G. Katz, MD, CMQ, FACS, FASCO, professor, chair, the Department of Surgical Oncology, the Division of Surgery, The University of Texas MD Anderson Cancer Center, discusses the efficacy of mFOLFIRINOX, a chemotherapy regimen consisting of oxaliplatin, irinotecan, leucovorin, and fluorouracil, prior to pancreatectomy in patients with borderline resectable pancreatic cancer.

The phase 2 A021501 trial (NCT02839343) aimed to investigate the efficacy of mFOLFIRINOX and the efficacy of mFOLFIRINOX followed by hypofractionated radiation therapy, with a primary end point of 18-month overall survival (OS) compared with a preselected historical OS control rate of 50%. Accrual to the radiation therapy arm closed early due to futility. The neoadjuvant mFOLFIRINOX alone arm demonstrated a Kaplan-Meier–estimated 18-month survival rate of 66.7%, exceeding the control rate.

The chemotherapy-alone arm was associated with a median OS of 29.8 months, Katz says. This arm of the A021501 trial showed a survival rate superior to the historical control rate, confirming that neoadjuvant mFOLFIRINOX should be further studied in pancreatic cancer, such as in combination with novel therapeutics, Katz explains.

Since the radiation arm did not fully accrue, it could not be statistically evaluated, so the role of neoadjuvant radiation therapy in pancreatic cancer is still unclear, Katz concludes.

Matthew H. G. Katz, MD, CMQ, FACS, FASCO, discusses the efficacy of mFOLFIRINOX, a chemotherapy regimen consisting of oxaliplatin, irinotecan, leucovorin, and fluorouracil, prior to pancreatectomy in patients with borderline resectable pancreatic cancer.

Dr. Katz on Neoadjuvant mFOLFIRINOX in Pancreatic Cancer

Jacob G. Scott, MD, DPhil, associate staff, Departments of Translational Hematology and Oncology Research and Radiation Oncology, Cleveland Clinic, clinical assistant professor, Department of Molecular Medicine, adjunct assistant professor, Department of Physics, Case Western Reserve University School of Medicine, member, Developmental Therapeutics Program, Case Comprehensive Cancer Center, Case Western Reserve University, discusses the rationale to evaluate genomic-adjusted radiation dose (GARD)–based radiotherapy dosing in oncology.

Many patients with cancer who require radiation therapy receive a 5-to-6-week treatment schedule of radiation dosed at around 2 Gy per day, Scott says. However, patients have varied responses to this approach.

Notably, GARD-based radiotherapy dosing quantitatively predicts for how well a patient may benefit from radiation given at a particular dose, Scott explains.

Findings from a recent cohort-based pooled analysis that were published in 

 demonstrated that the biological effect of GARD-quantified radiotherapy is associated with time to first recurrence and overall survival in patients with cancer who received radiation therapy, Scott concludes. 

Jacob G. Scott, MD, DPhil, discusses the rationale to evaluate genomic-adjusted radiation dose–based radiotherapy dosing in oncology.  



Onc Club | Videos

Dr Shah on Outcomes With Checkpoint Inhibition in Patients With Cancer and Pre-Existing Neurologic Autoimmune Disorders

Dr. Katz on Neoadjuvant mFOLFIRINOX in Pancreatic Cancer

Dr. Scott on the Rationale to Evaluate GARD-Based Radiotherapy Dosing in Oncology