Case Report: PD-1 Inhibitor Is Active in Lung Adenocarcinoma With B Cell Deficiency

Abstract

Introduction: In murine cancer models, B cells are unnecessary for efficacy of PD-1 inhibitor. However, we do not know whether this applies to clinical settings, especially in patients with non-small-cell lung carcinoma (NSCLC). Case presentation: We report on the case of an advanced lung adenocarcinoma patient without oncogenic driver mutations whose disease progressed on second-line bevacizumab-containing chemotherapy regimens. These previous treatments resulted in profound thrombocytopenia and increased number of B cells; both effects were hard to alleviate. The patient was diagnosed with marginal zone B-cell lymphoma by flow cytometry immunophenotyping. After five cycles of rituximab in combination with lenalidomide treatment, the percentage of B cells rapidly declined to undetectable levels and the lymphoma regressed completely. However, because masses in the lung gradually increased, this patient was subsequently treated with a PD-1 inhibitor. The patient's condition stabilized, and the mass shrank to reach partial response, with progression free survival exceeding 15 months and no serious adverse events. Conclusion: The present case proves the efficacy of PD-1 inhibitor in metastatic lung adenocarcinoma in the absence of B cells. Immune checkpoint inhibitions are thus a choice for patients with B cell deficiencies, such as X-linked agammaglobulinemia, immunoglobulin deficiencies, and common variable immunodeficiency, diseases that have historically been excluded from clinical trials for oncologic drugs.

Successful treatment of lung cancer coexisting with B‑cell lymphoma with pembrolizumab following rituximab‑included chemotherapy: A case report

“…To date, only a few cases of advanced lung cancer with B-cell lymphoma have been reported. Two of these cases were successfully treated with alectinib or osimertinib ( 10 , 11 ) whereas the other cases reported partial efficacy of sintilimab treatment and exacerbation after pembrolizumab treatment in patients with advanced lung cancer and B-cell lymphoma ( 2 ) To the best of our knowledge, this is the first report of pembrolizumab treatment following one course of BR therapy for advanced NSCLC accompanied by MALT lymphoma, which resulted in good disease control.…”

“…Three reports have investigated the treatment of B-cell lymphoma complicated with other solid cancers with ICIs ( Table I ). Two studies reported that MALT lymphoma with solid tumors was controlled by ICI treatment followed by rituximab monotherapy or rituximab-included chemotherapy ( 2 , 9 ) and one of which achieved CR for MALT lymphoma and PR for lung cancer by treatment with five courses of rituximab-included regimen, followed by sintilimab monotherapy ( 2 ). Another study reported CR for MALT lymphoma that developed during pembrolizumab treatment for urothelial cell carcinoma and was treated with four courses of rituximab ( 9 ) These cases suggest that ICIs with rituximab-containing regimens may be effective in these populations.…”

“…The efficacy of three courses of BR therapy for MALT lymphoma has been reported to be high, with an ORR of 100% and long-term response ( 15 ) One cycle of BR therapy may be effective enough to prevent relapse or recurrence after pembrolizumab initiation. Considering cases of MALT lymphoma with no relapse or exacerbation after ICI treatment ( 2 , 9 ) the initiation of ICI treatment may be safe after CR is achieved with a rituximab-containing treatment.…”

“…The majority of previous reports regarding such cases included accidental diagnoses or successful treatments through surgical resection ( 1 ). However, cases of advanced lung carcinoma and B-cell lymphoma being treated by immune checkpoint inhibitors (ICIs) have rarely been reported, except for two cases with conflicting results involving treatment with sintilimab and pembrolizumab ( 2 , 3 ).…”

Durvalumab-induced thyroiditis in a patient with non-small cell lung carcinoma: a case report and review of pathogenic mechanisms

“…An alternative way to study the role of the humoral pathway would be to evaluate ICI in different types of B-cell deficiency. For example, it was demonstrated in murine studies (with B-cell depleting antibodies or strains lacking mature B-cells) that the presence of B-cells is not required for a tumour response to anti-PD-1 therapy [ 40 ]. In a patient with hypogammaglobulinemia after rituximab treatment (for marginal zone B-cell lymphoma), a partial response of the PD-1 inhibitor sintilimab was observed in advanced lung adenocarcinoma (co-existing in the same patient) [ 41 ].…”