Background

Cancer-associated thrombotic microangiopathy (CA-TMA) is a rare condition with high mortality. Unlike thrombotic thrombocytopenic purpura (TTP), CA-TMA does not tend to respond to plasma exchange (PEX); the only therapy to reduce mortality and organ damage is chemotherapy. Patients with CA-TMA are historically exposed to unnecessary PEX and delays of definitive therapy. With faster ADAMTS13 turnaround and better understanding of CA-TMA, we sought to examine the treatment pattern and outcomes of CA-TMA in a large Canadian province over the past 15 years.

Objectives

Describe CA-TMA treatment patterns and outcomes in newly diagnosed vs known cancer.

Methods

This retrospective cohort study included all adults diagnosed with CA-TMA in Alberta, Canada (2008-2023). CA-TMA was defined as microangiopathic hemolytic anemia and thrombocytopenia, without alternative explanations such as ADAMTS13 deficiency <10%, hemolytic-uremic syndrome, disseminated intravascular coagulation, and active infections. We examined quality of care measures including inappropriate ordering of ADAMTS13 in low-risk patients, rates and duration of PEX, oncology consultation and initiation of chemotherapy in-hospital or within 30 days of discharge. Outcome measures included overall survival (OS), length of stay (LOS), and TMA response, stratified by newly diagnosed vs known cancer, and by treatment regimen. Kaplan-Meier curves were used to estimate OS, differences were assessed using the log-rank test.

Results

Twenty-five patients presented with CA-TMA at a median age of 57 years, 14 (56%) were female. Nine (36%) had newly diagnosed cancer at the time of presentation, 9 (36%) had stable disease on chemotherapy, and 7 (28%) had progressive or relapsed cancer. Eighteen patients (72%) had metastatic cancer. Organ involvement included renal (11; 44%), neurological (10; 40%), and cardiac (3; 12%) dysfunction. ADAMTS13 assay was ordered in 4/9 (44%) patients with low-risk, 5/9 (56%) with intermediate and 5/7 (71%) with high-risk PLASMIC scores. ADAMTS13 was sent in 1/10 (10%) of cases between 2008-2013, 8/9 (90%) of cases (2014-2018), and 4/5 (80%) cases (2019-2023). Median ADAMTS13 turnaround time was 2.9 days (IQR 1.6-4.1).

The median LOS was 14 days; 11 (44%) patients required ICU admission. Only 13 (52%) received oncology consult within 30 days. ECOG status was documented in only 11 (44%), with ECOG 0-1 in 10/11 (91%). Treatment included: PEX in 15 (60%; including 7 without ADAMTS13 assays), chemotherapy in 5 (20%), immunosuppressive therapy (IST) in 4 (16%), cessation of inciting medications in 6 (24%), and transfusions in 4 (16%). None received eculizumab or plasma infusions alone. Prolonged PEX was common (median 5 PEX sessions), consuming 68 units of plasma. TMA response was achieved in 8 (32%): PEX + chemotherapy (n=3), PEX ± IST (n=3), medication discontinuation (n=2). At a median follow-up time of 22 days (IQR 8-127), 24 (96%) died: 13 (52%) died in-hospital, 4 (16%) <30 days of discharge, while 8 (32%) survived >3 months. Most patients (12; 50%) died from underlying cancer ± TMA, followed by TMA (5; 21%) and bleeding (4; 17%).

There was no significant difference in age, goals of care, and proportion of new cancer diagnosis between those who received chemotherapy and those who did. Chemotherapy recipients trended towards higher rates of early oncology consult (80% vs 45%, P=0.20), TMA response (60% vs 35%, P=0.52) and longer OS (median 127 vs 14 days from TMA presentation, P=0.40). Early oncology consult was offered in only 2/9 (22%) patients with newly diagnosed cancer compared with 10/16 (63%) patients with known cancer (P=0.31). Chemotherapy was offered in 2/9 (22%) in both newly diagnosed and stable disease groups, and none in those with progressive disease. Median OS was significantly shorter in newly diagnosed and progressive disease than stable disease (14 vs 419 days, P=0.02).

Conclusion

We identified suboptimal management of CA-TMA including high rates of PEX and dismal rates of oncology consult and chemotherapy, especially in newly diagnosed cancers. This is alarming as over a third of our cohort had newly diagnosed cancer, who had much poorer OS compared with those with stable disease on chemotherapy. Rationale for treatment decisions cannot be ascertained due to limitations of retrospective study. Future prospective studies will better assess the treatment strategies and outcomes in CA-TMA.

Disclosures

Sun:CSL Behring; Pfizer; Roche; Sobi: Consultancy.

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2024
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