Grade 4 Thrombocytopenia during Treatment with High-Dose Interleukin-2 Is a Predictor of Response in Melanoma but Not in Renal Cell Cancer

Bael, Timothy E.; Peterson, Bercedis L.; Rasheed, Karima; Thoreson, M.; Gollob, Jared

doi:10.1097/00002371-200411000-00051

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“…A few other studies have evaluated the relationship between platelet nadir and response to IL-2 therapy with conflicting results (American Cancer Society 2014 ; Rosenberg et al 1998 ; Klapper et al 2008 ; MacFarlane et al 1995 ; Royal et al 1996 ; Bael et al 2004 ). Some studies (American Cancer Society 2014 ; Rosenberg et al 1998 ; MacFarlane et al 1995 ) have shown no significant association between degree of thrombocytopenia and response while others (Klapper et al 2008 ; Royal et al 1996 ; Bael et al 2004 ) have demonstrated an association between platelet nadir and response. The precise mechanism of development of marked thrombocytopenia in association with response to IL-2 has not been conclusively elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…The precise mechanism of development of marked thrombocytopenia in association with response to IL-2 has not been conclusively elucidated. Proposed mechanisms include more adept platelet activation through the inflammatory cascade or mediation of an antibody-producing immune response (MacFarlane et al 1995 ; Bael et al 2004 ). The latter has been suggested as platelets share common antigens with melanoma tumor cells including glycoprotein IIb/IIIa, CD63 and vitronectin receptor α V β 3.…”

Section: Discussionmentioning

confidence: 99%

“…The latter has been suggested as platelets share common antigens with melanoma tumor cells including glycoprotein IIb/IIIa, CD63 and vitronectin receptor α V β 3. Antibody production against these common antigens may produce an autoimmune thrombocytopenia and concurrent anti-tumor effect (Bael et al 2004 ).…”

Section: Discussionmentioning

confidence: 99%

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Clinical characteristics and treatment-related biomarkers associated with response to high-dose interleukin-2 in metastatic melanoma and renal cell carcinoma: retrospective analysis of an academic community hospital’s experience

et al. 2015

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BackgroundImmunotherapy in the treatment of metastatic melanoma and renal cell carcinoma can produce durable therapeutic responses, which may improve survival. We aimed to identify clinical characteristics and biomarkers associated with response to high-dose interleukin-2 therapy (IL-2) in patients with metastatic melanoma and renal cell carcinoma treated at an academic community hospital.Patients/MethodsWe retrospectively analyzed clinical variables and biomarkers of 50 consecutive metastatic melanoma or renal cell carcinoma patients treated at our institution with IL-2 during 2004 – 2012. We evaluated clinical characteristics: metastatic sites of disease, prior therapies, number of IL-2 doses per cycle, response duration, autoimmune phenomena, and peak fever, as well as laboratory biomarkers: baseline LDH, platelet nadir, and baseline and highest absolute lymphocyte count (ALC). Survival outcomes were calculated using Kaplan-Meier curves.ResultsVariables differing between responders (clinical benefit group) and non-responders (no clinical benefit group) in metastatic melanoma included platelet nadir during treatment (p = 0.015), autoimmune phenomena (p = 0.049), and in renal cell carcinoma, platelet nadir (p = 0.026). There were no significant differences between number of doses of IL-2 received per cycle and response in either cancer subtype. Clinical benefit occurred in 25% of patients (9/36) when IL-2 was given as first-line therapy. Median overall survival for the clinical benefit group from the initiation of IL-2 to death or last follow-up was 61 months versus 17 months for the no clinical benefit group (p < 0.001) for metastatic melanoma. In renal cell carcinoma overall survival for clinical benefit patients was 48 months versus 17 months. No treatment-related deaths occurred.ConclusionsHigh-dose IL-2 can be safely administered by an experienced team in a non–intensive care oncology unit. The clinical benefit group developed autoimmune phenomena (melanoma patients), lower platelet nadir, and on average, received the same number of IL-2 doses as the no clinical benefit group, suggesting a response relationship to the patient’s baseline immune status. Further investigation of immune predictors of response may be useful to select appropriate patients for this therapy.

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