The ethics of immunotherapy access: Beyond regulatory approvals in resource-constrained settings

INTRODUCTION

India faces an unprecedented cancer burden, with an estimated 1.57 million new cases expected in 2025.^[1] With one oncologist for every two thousand patients, the country is at the center of an ethical and access crisis. Despite remarkable advances in immuno-oncology, only 15–20% of eligible patients receive checkpoint inhibitors, largely because of economic, regulatory, and structural barriers.^[2,3] This gap has created a silent epidemic of what may be described as systemic logistic toxicity. The impact is not only biological, but also economic and temporal. The cost of a single pembrolizumab cycle exceeds the annual income of nearly 70% of Indian households, earning <USD 3,000. Meanwhile, radiotherapy utilization remains at 28.5%, far below the Indian Council of Medical Research (ICMR) benchmark of 58.4%.^[4,5] Such disparities can lead to treatment delays, denial, and preventable deaths.^[6]

This editorial is directed toward clinicians, administrators, and policymakers. It advocates an ethics-driven, low-dose immunotherapy model that combines affordability with scientific rigor. Access to cancer immunotherapy should not be a privilege determined by wealth but a right grounded in human dignity.

THE EMERGING LOW DOSE PARADIGM

India’s strength in generic medicine production provides a solid foundation for flexible regulation and innovative approaches for affordable treatment. The central proposal is to adopt evidence-based, low-dose regimens under nationally regulated, off-label frameworks. This ensured transparency and fair access.^[7,8] Promising examples at Tata Memorial Hospital with a low-dose nivolumab protocol using 20 mg every 3 weeks for advanced head-and-neck cancer achieved a 1-year overall survival of 43.4%, with a hazard ratio (HR) of 0.545. Cost savings reached 75% through vial-sharing strategies. Similarly, the All India Institute of Medical Sciences PLANeT trial using pembrolizumab 50 mg every 6 weeks in triple-negative breast cancer significantly improved pathological complete response rates with one-tenth the cost. This approach was recognized by the European Society for Medical Oncology 2025 as a model for resource-constrained settings.^[9]

China’s experience with domestically developed PD-1 inhibitors offers valuable lessons. They received 20 approvals and 80% local manufacturing. The adoption rates now exceed 70% at prices that are only 20–30% of those in the United States. For example, pembrolizumab costs approximately USD 2,492 in China compared to over USD 10,000 in the United States. Access to these trials is more limited in low-income and middle-income countries (LMICs), which account for 70% of all cancer-related deaths globally. However, up to 90% of clinical trials originate from high-income countries (HICs), and approximately 80% of trial participants are from HICs. Only 8% of oncology trials were led by investigators from LMICs, and only one-third of the trials enrolled patients from LMICs.^[10]

ETHICAL STEWARDSHIP

The ethical stewardship of immunotherapy in resource-limited settings must rest on the principles of beneficence, non-maleficence, autonomy, and justice.^[11] Treatments should be grounded in solid evidence, cost transparency, and equitable access. India already has a regulatory framework that supports the compassionate and clinician-led use of immunotherapy. The 2017 ICMR patient-centered guidelines, the 2019 New Drugs and Clinical Trials Rules, and oversight of institutional ethics committees together enable safe off-label prescribing. However, major policy gaps persist. Biologic agents remain outside the control of the National Pharmaceutical Pricing Authority and Drug Price Control Order. Combined with 10–20% import duties and goods and services taxes, these exemptions raise the cost of treatment by 15–25%, excluding up to 85% of patients who might otherwise benefit.^[12]

As cancer incidence is projected to exceed four million by 2045, India must focus on indigenous research and greater public funding. The success of immuno ACT’s NexCAR19 CAR T-cell therapy, priced at USD 35,000 compared to USD 400,000 globally, demonstrates that high-impact innovation is possible within India’s ecosystem. Increasing healthcare spending from 1.84% to 2.5% of the GDP by 2026 would strengthen domestic biosimilar development and expand patient assistance programs.^[13]

BUILDING LMIC BENCHMARKS

Therefore, low-dose immunotherapy should be guided by disease-specific data and real-world outcomes. National registries capturing tumor characteristics, biomarker profiles, immune-related adverse events, and survival results will be crucial in developing an evidence-based suited to the realities of LMICs. National standard operating procedures now require multidisciplinary decision-making, LMIC-specific dossiers, transparent documentation, institutional ethics approvals, pharmacovigilance linkages, and long-term follow-up audits.^[14] These measures enhance integrity and accountability while prohibiting promotional use. Table 1^[15-26] enumerates emerging low-cost immunotherapy strategies in various systemic settings.

The Ayushman Bharat scheme, which provides INR 5 lakh of coverage per family, must now include low-dose and novel immunotherapies.^[27] The 2025 Union Budget introduced duty waivers on 36 cancer drugs, including a goods and services tax reduction on durvalumab. However, domestic innovation, such as the Phase 1 immunotherapy program at the performance grading index, still requires sustained fiscal and policy support.

PRECISION MEETS EQUITY

Precision oncology and equitable access should function as complementary priorities rather than competing priorities. Monotherapy should be prioritized for programmed death-ligand-1 high non-small cell lung cancer, while combination regimens should target esophageal and nasopharyngeal carcinomas, where robust survival gains have been demonstrated with HRs between 0.52 and 0.69.^[16] Therapy in biomarker-negative or late-line settings without supporting evidence should be avoided to conserve limited resources. China’s bispecific antibody Ivonescimab in HARMONi-2 trial showed a PFS HR of 0.51, which reflects innovation aligned with cost reforms can achieve global competitiveness.^[23] India should apply similar lessons to shape its precision-equity strategy.

FROM POLICY TO PRACTICE: A NATIONAL SHIFT

Ethical access to immunotherapy requires that innovation be evaluated not only on clinical efficacy but also on cost-effectiveness and systemic impact. The development of drugs should focus on significant improvements in survival and quality of life. Convenience in dosing or administration is a valid patient outcome. However, when it drives huge price premiums, it risks diverting investment toward marginal formulation changes rather than genuinely new or affordable therapies. In resource-constrained settings, payers and regulators must use unambiguous, evidence-based criteria. This is done to decide when an added benefit deserves greater expenditures while ensuring equality in these decisions.^[28]

To make this vision a reality, clinicians must be responsible for developing and implementing national and institutional guidelines that promote best practices. There should be specific guidelines for compassionate access pathways, including who is eligible to use them and how they will be implemented. Low-dose regimens should be validated in advance and included in guidelines, with safeguards in place for doctors who use them, provided the data support their use. Digital platforms can facilitate easier tracking of consent, toxicity, and interdisciplinary review by maintaining a record that can be easily accessed and verified. Policy levers must align with these clinical efforts. Biologic price caps based on successful small molecule frameworks, along with duty exemptions for key oncology medications, can alter how people perceive prices. Expansion of teleoncology networks and regionally organized tumor boards can narrow geographic gaps in expertise and access. A long-term sustainability is enhanced by allocating more funds to local research and development. India is a global hub for cheap generics, so it has both moral and financial responsibilities. Scaling indigenous programs such as NexCAR19 and promoting organized international collaboration can gradually transform immunotherapy and CART cell therapy from an elite therapeutic option to a standard of care that benefits patients from all walks of life.

CONCLUSION

India is at a critical point in the global fight against cancer. The combination of low-dose science, homegrown innovation, and ethical regulation offers a transformative opportunity to redefine how the world delivers immunotherapy. This is not merely an aspiration, but a moral imperative to ensure that survival is defined by scientific evidence and equitable access, not by geography or wealth.