Comparison of Immunohistochemistry With Fluorescence In Situ Hybridization for Assessment of CCND1 Rearrangement in Plasma Cell Myeloma

More than half of patients with plasma cell myeloma (PCM) relapse after treatment and require novel therapies. Venetoclax, a highly specific and effective oral BCL2 inhibitor, has a favorable risk-benefit ratio for PCM patients with t(11;14)/ IGH::CCND1. Standard of care for new or relapsed cases of PCM incorporates fluorescence in situ hybridization (FISH) analysis for the detection of IGH::CCND1. However, FISH requires a high-quality bone marrow (BM) aspirate sample and plasma cell (PC) purification. Immunohistochemical (IHC) staining to detect overexpressed cyclin D1 protein resulting from IGH::CCND1 is lower cost, more widely available, and has a faster turnaround time than FISH. However, a predictive cyclin D1 IHC cutoff has yet to be established for correlation with IGH::CCND1. We evaluated a testing cohort of 85 BM biopsy cases diagnosed as PCM with adequate core biopsies and corresponding myeloma FISH results (43 fusion positive and 42 fusion negative) to develop a multitiered classification system for cyclin D1 IHC expression in plasma cell myeloma that can predict IGH::CCND1 fusion status with high confidence in the majority of cases. Using H-score to predict fusion status yielded positive and negative predictive values of 97% and 100%, respectively. A validation cohort consisting of 50 additional cases (24 fusion negative and 26 fusion positive) had 93% positive and 100% negative predictive values for fusion status. We find that cyclin D1 IHC has high concordance with FISH for IGH:: CCND1 fusion status and is a valuable alternative when FISH is suboptimal or unavailable.