New VTE incidence ‘significant’ after CAR T-cell therapy for lymphoma
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ORLANDO — More than one in 10 patients with lymphoma who underwent chimeric antigen receptor T-cell therapy developed new venous thromboembolism, according to study results presented at TCT | Transplantation & Cellular Therapy Meetings.
Researchers characterized this as a “significant incidence” of new VTE; however, they noted most patients could be managed with therapeutic anticoagulation without bleeding complications.
“Given the numbers of patients who develop a new clot after infusion, it is important to investigate this further,” Hamza Hashmi, MD, clinical fellow in the blood and marrow transplant and cellular immunotherapy program at Moffitt Cancer Center, told Healio. “ This can have significant implications on the management of these patients, especially after they get CAR T-cell therapy and lymphodepleting chemotherapy, which can drop their platelet counts.”
Cancer-associated VTE is a major cause of morbidity and mortality for patients with hematologic malignancies. However, data are limited on the frequency and management of VTE among patients who undergo CAR T-cell therapy.
Hashmi and colleagues conducted a single-center retrospective study to evaluate the incidence and characteristics of VTE and use of anticoagulation use for patients with lymphoma who underwent CAR T-cell therapy.
The analysis included 148 patients who received CD19-directed CAR T-cell therapy for aggressive B-cell lymphomas between May 2015 and September 2019.
The majority were men (62%) and aged older than 60 years (63%). Most (77%) had stage III or stage IV disease, and 18% had ECOG performance status of 2 to 4.
Researchers assessed both recent VTE —diagnosed within 6 months prior to CAR T-cell therapy — and new VTE, diagnosed in the first 100 days after infusion.
Twenty-eight patients (19%) had known VTE prior to CAR T-cell infusion. These included 17 cases of deep vein thrombosis alone, one case of pulmonary embolism alone, seven cases of DVT plus PE, and three cases of splenic vein thrombosis.
Twelve of these 28 patients continued anticoagulation after infusion. Six had anticoagulation held because of low platelet count within the first 100 days after infusion (median, 5 days; range, 2-7). Median platelet counts were 54,000/uL (range, 39,000-116,000) when anticoagulation was held and 66,000 uL (range, 54,000-213,000) when it was resumed. One patient developed recurrent thrombosis while anticoagulation was held.
Sixteen (58%) of the 28 patients with known VTE had anticoagulation held prior to infusion, and two of them developed a new VTE within 100 days after CAR T-cell infusion.
Sixteen patients (11%) in the overall cohort developed a new VTE within 100 days after infusion. This included two of the patients with known VTE who had anticoagulation held after infusion.
VTE incidents in this group included eight cases of DVT, four cases of PE, and four other thromboses (eg, cerebral, mesenteric or renal). Eleven cases were symptomatic, five were incidental and four were catheter-related.
Twelve of these 16 patients started anticoagulation with dalteparin (n = 4), low-molecular weight heparin (n = 2), unfractionated heparin (n = 2), rivaroxaban (Xarelto, Janssen; n = 2), apixaban (Eliquis; Bristol-Myers Squibb, Pfizer; n = 1) or dabigatran (Pradaxa, Boehringer Ingelheim; n = 1).
Five had anticoagulation held at a median 5 days (range, 3-10) after initiation because of low platelet count, but two resumed after initial interruption. Median platelet count at the time of anticoagulation hold was 53,000/uL (range, 39,000-202,000) and median count at anticoagulation resumption was 58,000/uL (range, 55,000-61,000).
Researchers reported no major bleeding events among patients in either group who continued on therapeutic anticoagulation.
The findings suggest interruption of anticoagulation for platelet count less than 50,000/uL and resumption of anticoagulation once platelet count is greater than 50,000/uL is a safe practice, researchers concluded.
“It’s not always feasible or possible to continue anticoagulation, so the question of what is the safe number at which you can hold anticoagulation without any recurring events becomes really important,” Hashmi said. “We need to continue to investigate this in a larger data set and see if the numbers are consistent.” – by Mark Leiser
Reference: Hashmi H, et al. Abstract 399. Presented at: TCT | Transplantation & Cellular Therapy Meetings; Feb. 19-23, 2020; Orlando.
Disclosures: The authors report no relevant financial disclosures.