RESUMEN
Polatuzumab vedotin (Pola) is an approved therapy in combination with rituximab and bendamustine for relapsed or refractory diffuse large B-cell lymphoma (RR-DLBCL) based on positive results of the landmark phase II randomised G029365 trial. However, trial results for many approved novel therapies in RR-DLBCL have not been replicated in routine care cohorts, as RR-DLBCL patient populations are heterogeneous and trial eligibility is increasingly restrictive. We evaluated outcomes from pola ± bendamustine and rituximab in patients with RR-DLBCL enrolled in a compassionate access program with no alternative treatment options identified via the Australasian Lymphoma and Related Diseases Registry according to their eligibility for the original phase II published study. Of 58 eligible patients, 74% met the criteria deeming them ineligible for the G029365 original study at the time of pola's commencement. Median progression-free survival and overall survival in our cohort were 2.3 and 3.5 months, respectively. In contrast to the landmark trial cohort, more of our patients ceased therapy prior to completion, the majority due to progressive disease and only 8/58 received any subsequent treatment. Dismal outcomes in this Australian real-world population demonstrate trial eligibility is challenging to meet, and newer treatments can be difficult to deliver in routine care. Clinically applicable results from therapeutic studies require trial cohorts to reflect representative clinical populations wherever possible, and more research is required to address the benefit of novel agents in the increasing majority who are ineligible for modern studies.
RESUMEN
BACKGROUND: Direct acting oral anticoagulants (DOAC) are now commonly prescribed medications. Urgent reversal of their anticoagulant effect is sometimes required in emergency situations. In Australia, a specific reversal agent for factor Xa (FXa)-inhibitor DOAC is not available. Instead, two non-specific haemostatic agents, activated prothrombin complex concentrate (aPCC) and 3 factor-prothrombin complex concentrate (3F-PCC), are used off-label despite a paucity of evidence for their effectiveness or safety. AIMS: To provide further insight into the efficacy and safety of 3F-PCC and aPCC for the reversal of the anticoagulant effect of FXa inhibitor DOACs. METHODS: We conducted a single-centre retrospective cohort study to investigate the use of aPCC and 3F-PCC for patients on FXa-inhibitor DOAC who present with a significant bleeding event or who require urgent surgery. The primary outcome was haemostatic efficacy according to prespecified criteria. Safety outcomes included the thromboembolic event rate and all-cause mortality during the hospital admission. RESULTS: A total of 51 patients was included in the study (36 patients who had a spontaneous bleeding event and 15 non-bleeding patients who required urgent perioperative management). Thirty-one patients received aPCC and 20 patients received 3F-PCC. Haemostasis was adjudicated as effective in all assessable patients (n = 50; 100%). Thromboembolic events occurred in three patients who received aPCC and one patient who received 3F-PCC. All-cause mortality was 7.8% (four patients). CONCLUSIONS: Both aPCC and 3F-PCC are useful adjuncts for the management of patients who require urgent reversal of the anticoagulant effect of FXa-inhibitor DOAC. However, the risk of thromboembolism in this patient group requires careful consideration. Prospective, comparator studies are needed along with the development of guidelines that reflect the availability of haemostatic agents in Australia.
