Abstract PO5-20-10: Treatment with CDK4/6 Inhibitor in a Patient with Metastatic Breast Cancer Causing Myelophthisis
Authors: Dahake Nikita , Senchak Jordan , Nasibli Jalil , Incorvati Jason 
Published: May 2024

Abstract
Background: Symptomatic bone marrow metastasis causing myelophthisis is a rare manifestation of metastatic breast cancer, indicating a poor prognosis due to significant cytopenias. CDK4/6 inhibitors are first-line therapies for metastatic hormone-positive breast cancer but remain an unclear choice in breast cancer patients with significant cytopenias due to associated hematological adverse effects. We present a case of biopsy-proven hormone-positive breast cancer with bone marrow infiltration causing profound pancytopenia. CDK4/6 inhibitors were safely administered despite their cytopenic effects. Case Presentation: A 59-year-old female presented after an abnormal annual mammogram and biopsy showed calcifications stromal fibrosis, cyst formation, and usual ductal hyperplasia in the right upper outer quadrant. One month later, she presented to an outside hospital with gingival bleeding, epistaxis, progressive dyspnea on exertion, and generalized weakness. Labs showed severe anemia with a hemoglobin of 4.8 g/dL (baseline 12.1 g/dL), thrombocytopenia with platelets of 5 K/mm (baseline 215 K/mm), LDH of 879, reticulocyte count of 5%, and negative direct Coombs test. Peripheral smear showed no schistocytes, but showed nucleated RBCs, severely reduced platelets, and occasional giant platelets. The patient was treated for presumed ITP, and the presence of nucleated RBCs prompted bone marrow biopsy which confirmed metastatic invasive lobular carcinoma breast cancer (ER 90-95%, PR 90-95%, HER2 1+). She was discharged on letrozole 2.5 mg daily with close outpatient oncologic follow-up. One week later, she presented to our institution with persistent symptomatic anemia and thrombocytopenia. Inpatient systemic therapy was begun using dose-reduced Palbociclib (75mg) and letrozole with close CBC monitoring while also receiving packed red blood cells (goal &gt;6.5) and platelet transfusions (goal &gt;10). Repeat bone marrow biopsy showed extensive marrow fibrosis, but no significant hematopoietic elements. ADAMTS13 was 134%, ruling out TTP, and she was treated again for presumed ITP with dexamethasone and IVIG, Throughout the 4-week admission, her right breast mass decreased in size and she was discharged after completing 3 weeks of Palbociclib with biweekly outpatient transfusions. During follow-up, the patient’s hemoglobin and platelets slowly started to respond allowing her to become transfusion-independent and allowing dose escalation. Restaging scans 2 months after hospitalization showed an overall improvement of disease burden. The patient continued to do well for almost 18 months, however, later redeveloped visceral crisis and is responding to chemotherapy. Discussion: There is limited data on the management of breast cancer with bone marrow infiltration at presentation. A wide range of survival data in different case reports exists, ranging from 5 to 44 months. However, chemotherapy was used in these studies rather than CDK4/6 inhibitors. By far, cytopenias are the most concerning grade 3 and 4 side effect of Palbociclib. Data from the PALOMA-1 trial suggest that hematologic toxicities, specifically neutropenia, were different from those associated with cytotoxic chemotherapies and are more transient and reversible in nature. Studies have examined the in vitro mechanism of bone marrow suppression in Palbociclib versus cytotoxic chemotherapy, and its cytostatic effect on neutrophil precursors allows for hematological toxicities to be transient. With strong supportive care measures, patients in bone marrow visceral crisis can be safely treated with cytopenic CDK4/6 inhibitors.
Citation Format: Nikita Dahake, Jordan Senchak, Jalil Nasibli, Jason Incorvati. Treatment with CDK4/6 Inhibitor in a Patient with Metastatic Breast Cancer Causing Myelophthisis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-20-10.