Standard Chemotherapy Is ‘Suboptimal’ for Managing Myelosuppression in SCLC

Multilineage myelosuppression is a significant burden for patients treated with chemotherapy in a community oncology setting for extensive-stage small cell lung cancer (ES-SCLC), according to a retrospective cohort study published in Cancer Medicine.

"Results from this study suggest an unmet need for managing the burden of multilineage myelosuppression among patients receiving single-lineage supportive care," according to the study authors.

In a population of 1239 patients, 98.6% of patients experienced a myelosuppressive episode, and 48.6% experienced declines across all peripheral blood lineages throughout all lines of therapy. Among those with available data, 26.5% of patients experienced grade 3 neutropenia, 26.9% experienced grade 4 neutropenia, and 32.7% experienced grade 3 anemia. Grade 3 and 4 thrombocytopenia affected 31.0% and 16.1% of patients, respectively.

Neutropenia, thrombocytopenia, and/or anemia of grade 3 or higher in at least 2 lineages affected 33.9% of patients. Grade 3 or higher myelosuppressive episodes in all 3 lineages occurred in 15.5% of patients.

The vast majority of patients (94.0%) received supportive care during follow-up. The modalities included granulocyte colony-stimulating factor treatment (89.7%), intravenous volume expansion (52.1%), and erythropoiesis-stimulating agents (24.4%). In total, 32.6% of patients were eligible for red blood cell transfusion.

The vast majority (94.6%) of patients discontinued their frontline treatment regimen during follow-up, and the median time to discontinuation was 3.5 months.

“Results from this study suggest an unmet need for managing the burden of multilineage myelosuppression among patients receiving single-lineage supportive care,” the investigators wrote.

“Although frequently used, standard interventions for managing myelosuppressive [adverse effects] are suboptimal. As demonstrated in the high rates of cytopenia in more than one hematopoietic lineages, current supportive care measures that are lineage specific…do not address the burden of myelosuppression in other lineages. Additionally, each of these interventions imparts their own set of risks…. Also, these treatments do not proactively protect the bone marrow from chemotherapy-induced damage.”

Investigators of this retrospective cohort study analyzed toxicities in patients with ES-SCLC who received a chemotherapy regimen in a community oncology setting between September 2013 and November 2020. Additionally, 94.0% of patients began their frontline chemotherapy regimen at the index treatment date. Prior to therapy initiation, grade 3 or higher myelosuppressive events were uncommon: neutropenia affected 3.5% of patients, leukopenia affected 2.9%, lymphopenia affected 2.5%, anemia affected 1.6%, and thrombocytopenia affected 1.2%.

The mean follow-up was 10.4 months. Chronic pulmonary disease (5.5%), mild liver disease (2.3%), and renal disease (2.2%) were the most common non–cancer-related comorbidities from the Charlson Comorbidity Index.

The mean age in the study population was 66.9 years old, and most patients (62.7%) were 65 years or older. Additionally, 49.7% of patients were male. Most of the populationwas White (58.0%), and there was a small population of Black patients (2.2%). Most patients (64.5%) had an ECOG performance status of 0 or 1.

The study’s primary end point was the incidence of myelosuppressive episodes across all lines of therapy. Investigators defined episodes as all respective events occurring within 21 days of the first event, with the overall episode taking the highest observed event grade. Secondary end points included time to myelosuppressive episodes, treatment patterns, rates of supportive care use, and rates of eligibility for red blood cell transfusion.

In terms of grade 3 or higher toxicity, 20.6% of patients had anemia as well as neutropenia, 21.5% had anemia along with thrombocytopenia, and 22.8% had neutropenia along with thrombocytopenia.

The most common index regimens were platinum or etoposide-containing chemotherapy alone (64.3%) or platinum or etoposide-containing chemotherapy plus immuno-oncology treatment (22.4%).

Overall, 52.8% of patients received at least 1 subsequent line of therapy, and the median time to next therapy—measured from the start of index therapy—was 4.6 months. Patients received a median of 2 regimens. In total, 52.2% of the 2336 regimens received were platinum-based, and 8.1% contained topotecan (Hycamtin).

Potential limitations to this study, as noted by the investigators, included its retrospective nature and a lack of in-patient data, which may have produced underestimates of the incidence of myelosuppressive toxicities following hospital admission, as well as underestimates of supportive care use.

“The results of this study were based on data from community oncology settings and therefore may not be generalizable beyond this setting,” the investigators concluded. “Nonetheless, real-world data are likely to be representative of clinical experience across a broad distribution of patients and can provide valuable insight into everyday treatment patterns and health outcomes.”

Reference

Hart L, Ogbonnaya A, Boykin K, et al. Burden of chemotherapy-induced myelosuppression among patients with extensive-stage small cell lung cancer: a retrospective study from community oncology practices. Cancer Med. 2023;12(8):10020-10030. doi:10