GCSF prophylaxis is recommended in patients on chemotherapy with a >20% risk of febrile neutropenia and is to be considered if there is an intermediate risk of 10–20%. GCSF has been suggested as a possible adjunct to immunotherapy due to increased peripheral neutrophil recruitment and PD-L1 expression on neutrophils with GCSF use and greater tumour volume decrease with higher tumour GCSF expression. However, its potential to increase neutrophil counts and, thus, NLR values, could subsequently confer poorer prognoses on patients with advanced NSCLC. This analysis follows on from the retrospective multicentre observational cohort Spinnaker study on advanced NSCLC patients. The primary endpoints were OS and PFS. The secondary endpoints were the frequency and severity of AEs and irAEs. Patient information, including GCSF use and NLR values, was collected. A secondary comparison with matched follow-up duration was also undertaken. Three hundred and eight patients were included. Median OS was 13.4 months in patients given GCSF and 12.6 months in those not (p = 0.948). Median PFS was 7.3 months in patients given GCSF and 8.4 months in those not (p = 0.369). A total of 56% of patients receiving GCSF had Grade 1–2 AEs compared to 35% who did not receive GCSF (p = 0.004). Following an assessment with matched follow-up, 41% of patients given GCSF experienced Grade 1–2 irAEs compared to 23% of those not given GCSF (p = 0.023). GCSF prophylaxis use did not significantly affect overall or progression-free survival. Patients given GCSF prophylaxis were more likely to experience Grade 1–2 adverse effects and Grade 1–2 immunotherapy-related adverse effects.

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BackgroundThe Spinnaker study evaluated survival outcomes and prognostic factors in patients with advanced non-small-cell lung cancer receiving first-line chemoimmunotherapy in the real world. This sub-analysis assessed the immunotherapy-related adverse effects (irAEs) seen in this cohort, their impact on overall survival (OS) and progression-free survival (PFS), and related clinical factors.MethodsThe Spinnaker study was a retrospective multicentre observational cohort study of patients treated with first-line pembrolizumab plus platinum-based chemotherapy in six United Kingdom and one Swiss oncology centres. Data were collected on patient characteristics, survival outcomes, frequency and severity of irAEs, and peripheral immune-inflammatory blood markers, including the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII).ResultsA total of 308 patients were included; 132 (43%) experienced any grade irAE, 100 (32%) Grade 1–2, and 49 (16%) Grade 3–4 irAEs. The median OS in patients with any grade irAES was significantly longer (17.5 months [95% CI, 13.4–21.6 months]) than those without (10.1 months [95% CI, 8.3–12.0 months]) (p<0.001), either if Grade 1–2 (p=0.003) or Grade 3–4 irAEs (p=0.042). The median PFS in patients with any grade irAEs was significantly longer (10.1 months [95% CI, 9.0–11.2 months]) than those without (6.1 months [95% CI, 5.2–7.1 months]) (p<0.001), either if Grade 1–2 (p=0.011) or Grade 3–4 irAEs (p=0.036). A higher rate of irAEs of any grade and specifically Grade 1–2 irAEs correlated with NLR <4 (p=0.013 and p=0.018), SII <1,440 (p=0.029 ad p=0.039), response to treatment (p=0.001 and p=0.034), a higher rate of treatment discontinuation (p<0.00001 and p=0.041), and the NHS-Lung prognostic classes (p=0.002 and p=0.008).ConclusionsThese results confirm survival outcome benefits in patients with irAEs and suggest a higher likelihood of Grade 1–2 irAEs in patients with lower NLR or SII values or according to the NHS-Lung score.

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A 74-year-old man with no previous history of tuberculosis presented with malaise, pyrexia (39°C) and 35kg weight loss, 16 months after TURBT for transitional cell carcinoma of the bladder and BCG instillation. He was pancytopaenic (Hb 84, Plt 99, WCC 2.94) and CT imaging showed splenomegaly, small pleural effusions and a sinusoidal lesion which on biopsy was not malignant. He did not have any promiment lymphadenopathy or pulmonary consolidation. Autoimmune and HIV screening were negative (CD4 310 (57%)) and both TTE and TOE showed no vegetations. IGRA/Quantiferon-Gold testing was positive and bone marrow biopsy yielded granuloma but no AFB on histology. Standard quadruple therapy was commenced for suspected disseminated mycobacterial disease. Mycobacterial cultures of early morning urine, blood and bone marrow were all positive and later identified as BCG on whole genome sequencing, sensitive to Rifampicin, Isoniazid, Amikacin and Moxifloxacin with undetermined Ethambutol sensitivity. Fully compliant with treatment, he developed a solid part cystic irregular enhancing 35mmmass encasing his left internal carotid artery seven months into treatment. ϒ-IFN-axis testing showed adequate responses to IL12 and IFN stimulation. Biopsy revealed AFB-positive granulomata leading to additional steroids for a presumed paradoxical reaction as well as treatment intensification with Moxifloxacin and Amikacin whilst awaiting cultures, the latter of which was discontinued following negative culture results and clinical and radiological improvement. Paradoxical reactions occur not infrequently (2-23%) and can present delayed (14-270 days) following initiation of treatment. He gained 25kg and made an uneventful recovery having received 18 months of BCG treatment.