Managing Chemotherapy-Induced Myelosuppression in Small Cell Lung Cancer

Chemotherapy-induced myelosuppression (CIM) remains one of the most significant and underappreciated barriers to delivering optimal cancer treatment. For patients with small cell lung cancer (SCLC), the bone marrow toxicity that accompanies chemotherapy and immunotherapy regimens can derail treatment plans, reduce quality of life, and even disqualify patients from potentially life-saving clinical trials.

During a live Case-Based Roundtable, Mohamed K. Mohamed, MD, PhD, Cone Health Cancer Center, discusses the real-world burden of CIM and why the oncology field's historically reactive approach to managing these complications may no longer be sufficient. He highlights the profound impact myelosuppression has on patients' daily lives, healthcare resource utilization, and treatment outcomes, and makes the case for a more proactive strategy in preventing and addressing these toxicities before they compromise care.

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Targeted Oncology: When referring a patient for a lung cancer clinical trial, how often do you see them excluded due to their hematologic toxicities?

Mohamed K. Mohamed, MD, PhD: That's actually very common. You can give them the 4 cycles of chemoimmunotherapy, and then their bone marrow is gone by the fourth cycle. When you try to go to the second line, patients don't meet the criteria. We are reactive in our nature. If a patient has neutropenia, they get growth colony-stimulating factors [G-CSF]. If a patient has anemia or low platelets, they get a transfusion. [Historically], we have been reacting to the condition, not proactive in trying to prevent it.

What do you consider to be the biggest challenge with CIM?

Maintaining the wellbeing of the patient. They go through tough treatment. Chemotherapy for SCLC had not changed for 40 years until we had immunotherapy recently. For the last 20-plus years in SCLC, every time another agent was added or removed, nothing was better than platinum-etoposide. All other trials failed to show any effect.

What is the impact of CIM on the patient?

Myelosuppression is an issue for the patient, health care staff, and to the family of the patient. They have to bring them for treatment. Patients can end up in the hospital because of CIM.

[There was a survey of] 301 patients with solid tumors: breast, colorectal, and lung.¹ Eighty-eight percent felt that myelosuppression worsened their quality of life, and 79% required treatment for CIM. The impact of CIM on activities of daily living is significant: 36% said it had an impact on the ability to complete daily tasks within the home, 43% said their ability to work was affected, and 31% said their opportunities to socialize were affected. Even relationships with family or partners and taking a shower or brushing their teeth were affected by myelosuppression.²

[In a study of the impact of CIM on patients with SCLC], when you look at neutropenia by itself, around 45% of patients [with SCLC have grade ≥3 neutropenia].³ Anemia is 34%, and thrombocytopenia is 33%. But there are patients that will have 2 or all 3. Grade ≥3 [hematologic toxicity] is serious [not only] for the patient but also for the healthcare resource utilization. For patients with SCLC, all-cause hospitalization was 19%, and patients were in the hospital for 1 to 21 days. Over 10% of patients needed red blood cell transfusion, and 84% needed long-acting G-CSF.

How are providers reacting to and managing CIM?

Dose delays or reductions [are the most common reactions to CIM]. If a patient has significant neutropenia, anemia, or thrombocytopenia in the first cycle, we will delay the next cycle by a week or 2. Sometimes you cut the dose because you are already using primary prophylaxis. Reducing the dose is, of course, not as efficacious as using all of the treatment. G-CSF can be used as neutropenia prophylaxis, but there are adverse effects you get from that, like musculoskeletal pain. Erythropoiesis-stimulating agents and iron infusions can be used for anemia, but they increase the risk for thromboembolic events. Every one of these factors that we are reacting to has its own problem too. It’s not like it’s safe to get a blood transfusion.

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REFERENCES

1. Epstein RS, Aapro MS, Basu Roy UK, et al. Patient Burden and Real-World Management of Chemotherapy-Induced Myelosuppression: Results from an Online Survey of Patients with Solid Tumors. Adv Ther. 2020 Aug;37(8):3606-3618. doi: 10.1007/s12325-020-01419-6. Epub 2020 Jul 8. PMID: 32642965; PMCID: PMC7340862.

2. Epstein RS, Basu Roy UK, Aapro M, et al. Cancer Patients' Perspectives and Experiences of Chemotherapy-Induced Myelosuppression and Its Impact on Daily Life. Patient Prefer Adherence. 2021 Feb 25;15:453-465. doi: 10.2147/PPA.S292462. PMID: 33658769; PMCID: PMC7920579.

3. Goldschmidt J, Monnette A, Shi P, et al.Burden of chemotherapy-induced myelosuppression among patients with ES-SCLC in US community oncology settings. Future Oncol. 2022 Nov;18(35):3881-3894. doi: 10.2217/fon-2022-0754. Epub 2022 Nov 15. PMID: 36377828.