In the Journals

Immune perturbations may increase melanoma risk among certain non-Hodgkin's lymphoma survivors

Certain chemotherapeutic agents and immune-related medical conditions appeared to contribute to increased melanoma risk among older survivors of a specific non-Hodgkin’s lymphoma subtype, according to results of a retrospective study.

Although treatment advances in non-Hodgkin’s lymphoma have increased survival considerably during the past 4 decades, survivors — specifically those with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) — continue to demonstrate an increased risk for melanoma. The explanation for this elevated risk remains unknown.

Clara J.K. Lam, MD, of the radiation epidemiology branch of the NCI, and colleagues conducted this study to quantify whether non-Hodgkin’s lymphoma treatments and immune-related medical conditions appeared to influence melanoma risk.

The researchers used the SEER database to identify 44,870 individuals who were 1-year survivors of their first primary non-Hodgkin’s lymphoma. All patients were diagnosed between 1992 and 2009, and they were aged 66 to 83 years at diagnosis.

Researchers identified 202 cases of melanoma among all non-Hodgkin’s lymphoma survivors. Of these, 91 occurred in survivors of the CLL/SLL subtype and 111 occurred in survivors of other subtypes (cumulative incidence by age 85 years: CLL/SLL = 1.37%; other subtypes = 0.78%).

Among patients with the CLL/SLL subtype, melanoma risk appeared significantly elevated for those who received an infused chemotherapy regimen with or without rituximab (Rituxan; Genentech, Biogen Idec). Researchers calculated HRs of 1.92 (95% CI, 1.09-3.4) for those whose regimens included rituximab and 2.92 (95% CI, 1.42-6.01) for those whose regimens did not include rituximab.

Researchers also observed a significant risk elevation among patients who had T-cell activating autoimmune diseases diagnosed before CLL/SLL (HR = 2.27; 95% CI, 1.34-3.84) or after CLL/SLL (HR = 2.92; 95% CI, 1.66-5.12).

Among patients with other non-Hodgkin’s lymphoma subtypes, results demonstrated no association between melanoma risk and either specific treatments or T-cell/B-cell immune conditions.

Researchers acknowledged potential limitations of their study, including the lack of information about dose and length of chemotherapy treatment. Also, because data about oral chemotherapy agent usage were not available for the duration of the follow-up, the researchers were unable to test oral alkylators such as chlorambucil for a possible association with melanoma risk.

“Our study results provide direct evidence for the importance of immune perturbation in explaining the excess of melanoma diagnoses observed in survivors of CLL/SLL,” Lam and colleagues wrote. “Further research is needed to understand the biologic mechanisms behind the immune perturbations that lead to melanoma development and to determine if similar risks extend to younger survivors of non-Hodgkin’s lymphoma.” – by Anthony SanFilippo

Disclosure: The researchers report no relevant financial disclosures

Certain chemotherapeutic agents and immune-related medical conditions appeared to contribute to increased melanoma risk among older survivors of a specific non-Hodgkin’s lymphoma subtype, according to results of a retrospective study.

Although treatment advances in non-Hodgkin’s lymphoma have increased survival considerably during the past 4 decades, survivors — specifically those with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) — continue to demonstrate an increased risk for melanoma. The explanation for this elevated risk remains unknown.

Clara J.K. Lam, MD, of the radiation epidemiology branch of the NCI, and colleagues conducted this study to quantify whether non-Hodgkin’s lymphoma treatments and immune-related medical conditions appeared to influence melanoma risk.

The researchers used the SEER database to identify 44,870 individuals who were 1-year survivors of their first primary non-Hodgkin’s lymphoma. All patients were diagnosed between 1992 and 2009, and they were aged 66 to 83 years at diagnosis.

Researchers identified 202 cases of melanoma among all non-Hodgkin’s lymphoma survivors. Of these, 91 occurred in survivors of the CLL/SLL subtype and 111 occurred in survivors of other subtypes (cumulative incidence by age 85 years: CLL/SLL = 1.37%; other subtypes = 0.78%).

Among patients with the CLL/SLL subtype, melanoma risk appeared significantly elevated for those who received an infused chemotherapy regimen with or without rituximab (Rituxan; Genentech, Biogen Idec). Researchers calculated HRs of 1.92 (95% CI, 1.09-3.4) for those whose regimens included rituximab and 2.92 (95% CI, 1.42-6.01) for those whose regimens did not include rituximab.

Researchers also observed a significant risk elevation among patients who had T-cell activating autoimmune diseases diagnosed before CLL/SLL (HR = 2.27; 95% CI, 1.34-3.84) or after CLL/SLL (HR = 2.92; 95% CI, 1.66-5.12).

Among patients with other non-Hodgkin’s lymphoma subtypes, results demonstrated no association between melanoma risk and either specific treatments or T-cell/B-cell immune conditions.

Researchers acknowledged potential limitations of their study, including the lack of information about dose and length of chemotherapy treatment. Also, because data about oral chemotherapy agent usage were not available for the duration of the follow-up, the researchers were unable to test oral alkylators such as chlorambucil for a possible association with melanoma risk.

“Our study results provide direct evidence for the importance of immune perturbation in explaining the excess of melanoma diagnoses observed in survivors of CLL/SLL,” Lam and colleagues wrote. “Further research is needed to understand the biologic mechanisms behind the immune perturbations that lead to melanoma development and to determine if similar risks extend to younger survivors of non-Hodgkin’s lymphoma.” – by Anthony SanFilippo

Disclosure: The researchers report no relevant financial disclosures

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