Translational Evaluation of Combined Immunotherapeutic Strategies and Advanced Supportive Care in Reducing Treatment-Related Toxicities Among Patients with Solid Malignancies

• Agussalim

  Parepare School of Nursing, Makassar Health Polytechnic, Ministry of Health Republic of Indonesia, South Sulawesi, Indonesia

Background: Immune checkpoint inhibitors and combination immunotherapeutic regimens have substantially improved survival outcomes across advanced solid malignancies. However, treatment-related toxicities—particularly immune-related adverse events (irAEs)—frequently compromise therapeutic continuity, adherence, quality of life, and clinical benefit.

Objective: This translational investigation evaluates whether integrating immunotherapy with a structured, multidisciplinary advanced supportive care framework reduces treatment-associated toxicities.

Methods: A prospective multicenter longitudinal cohort study was conducted across accredited Type B hospitals in Indonesia, enrolling 500 patients with histologically confirmed advanced solid malignancies receiving PD-1/PD-L1-based immunotherapy or chemo-immunotherapy. All participants received standardized early toxicity surveillance, personalized nutritional optimization, and structured psychosocial support. Toxicity was graded using CTCAE v5.0. Outcomes were compared against institutionally established historical benchmarks derived from 412 comparable patients treated at participating centers during 2021–2022 prior to protocol implementation. Analytical approaches included mixed-effects regression, Kaplan–Meier estimation, multivariate logistic regression, and effect-size estimation with 95% confidence intervals.

Results: Severe (grade ≥3) treatment-related toxicity occurred in 18.0% of patients, representing a 30.8% relative reduction from the historical benchmark of 26.0% (risk difference −8.0%, 95% CI −12.1% to −3.9%, p<0.001). Hospitalization rate was 22.0% (27.9% relative reduction from benchmark, p<0.001). Treatment adherence (≥85% planned cycles completed) was 85.6% versus 72.3% historically (p<0.001). Early toxicity monitoring (β = −0.41, 95% CI −0.58 to −0.24, p<0.001), nutritional optimization (β = −0.36, 95% CI −0.52 to −0.20, p<0.001), and psychosocial support (β = −0.29, 95% CI −0.45 to −0.10, p = 0.003) were independent protective predictors.

Conclusion: Integrated proactive supportive care significantly ameliorates toxicity burden and improves tolerability. Systematic implementation alongside immunotherapy is recommended to optimize outcomes in routine oncology practice.

[1] Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 2015; 27(4): 450-461.

[2] Sharma P, Allison JP. The future of immune checkpoint therapy. Science 2015; 348(6230): 56-61.

[3] Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science 2018; 359(6382): 1350-1355.

[4] Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med 2018; 378(2): 158-168.

[5] Wang DY, Salem JE, Cohen JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review. JAMA Oncol 2018; 4(12): 1721-1728.

[6] Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events: ASCO guideline. J Clin Oncol 2018; 36(17): 1714-1768.

[7] Haanen JBAG, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO guidelines. Ann Oncol 2017; 28(Suppl 4): iv119-iv142.

[8] Puzanov I, Diab A, Abdallah K, et al. SITC consensus recommendations on toxicity management. J Immunother Cancer 2017; 5(1): 95.

[9] Basch E, Deal AM, Kris MG, et al. Electronic symptom monitoring during chemotherapy improves outcomes. J Clin Oncol 2017; 35(6): 557-565.

[10] Ferrell BR, Temel JS, Alesi ER, et al. Integration of palliative care into standard oncology: ASCO guideline update. J Clin Oncol 2017; 35(1): 96-112.

[11] Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for metastatic non-small-cell lung cancer. N Engl J Med 2010; 363(8): 733-742.

[12] Arends J, Bachmann P, Baracos V, et al. ESPEN guidelines on nutrition in cancer patients. Clin Nutr 2017; 36(1): 11-48.

[13] Muscaritoli M, Arends J, Bachmann P, et al. From guidelines to practice: roadmap for oncological nutrition care. Lancet Oncol 2021; 22(10): e403-e412.

[14] Denis F, Cormier S, Filleron T, et al. Electronic monitoring and survival in ICI-treated patients: randomized trial. Lancet 2019; 393(10174): 294-306.

[15] Kavalieratos D, Corbelli J, Zhang D, et al. Association between palliative care and outcomes: systematic review and meta-analysis. JAMA 2016; 316(20): 2104-2114.

[16] Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with high tumor mutational burden. N Engl J Med 2018; 378(22): 2093-2104.

[17] Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic NSCLC. N Engl J Med 2018; 378(22): 2078-2092.

[18] Schmid P, Adams S, Rugo HS, et al. Atezolizumab plus nab-paclitaxel in triple-negative breast cancer. N Engl J Med 2018; 379(22): 2108-2121.

[19] Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab versus monotherapy in melanoma. N Engl J Med 2015; 373(1): 23-34.

[20] Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015; 372(26): 2521-2532.

[21] Eggermont AMM, Blank CU, Mandala M, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med 2018; 378(19): 1789-1801.

[22] Weber JS, Minor DR, Drabkin HA, et al. Nivolumab versus chemotherapy in anti-CTLA-4-refractory melanoma. J Clin Oncol 2017; 35(7): 785-792.

[23] Michot JM, Bigenwald C, Champiat S, et al. Immune-related adverse events with checkpoint blockade: comprehensive review. Eur J Cancer 2016; 54: 139-148.

[24] Naidoo J, Page DB, Li BT, et al. Toxicities of anti-PD-1/PD-L1 antibodies. Ann Oncol 2015; 26(12): 2375-2391.

[25] Abdel-Rahman O, ElHalawani H, Fouad M. Risk of irAEs with checkpoint inhibitors: meta-analysis. Crit Rev Oncol Hematol 2016; 101: 117-128.

[26] Petrelli F, Aroldi A, Borgonovo K, et al. Chemo-immunotherapy for NSCLC: systematic review and meta-analysis. Clin Transl Oncol 2020; 22(1): 1-9.

[27] Cortellini A, Di Maio M, Nigro O, et al. irAEs and clinical outcomes in PD-1/PD-L1-treated NSCLC: meta-analysis of real-world studies. Oncologist 2019; 24(9): e933-e942.

[28] Di Maio M, Basch E, Dennis F, et al. Patient-reported outcomes in cancer trials: systematic review. Lancet Oncol 2020; 21(7): e338-e350.

[29] Hui D, Bruera E. Models of palliative care delivery in oncology. J Clin Oncol 2020; 38(9): 852-865.

[30] Smith TJ, Temin S, Alesi ER, et al. ASCO provisional opinion: integrating palliative care into oncology. J Clin Oncol 2012; 30(8): 880-887.

[31] Zhang W, Di H, Xia R, et al. PSMD14 drives clear cell renal cell carcinoma progression via JAK/STAT3 signaling. J Cancer Res Updates 2026; 15(1): 85-105.

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