Experiences with Glofitamab Administration following CAR T Therapy in Patients with Relapsed Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is a rare type of B-cell Non-Hodgkin lymphoma (NHL) affecting predominantly male patients. While complete remissions following first-line treatment are frequent, most patients ultimately relapse, with a usually aggressive further disease course. The use of cytarabine-comprising induction chemotherapy and autologous stem cell transplantation, Rituximab maintenance, Bruton's tyrosine kinase (BTK) inhibitors and CAR T therapy has substantially improved survival. Still, options for patients relapsing after CAR T therapy are limited and recommendations for the treatment of these patients are lacking. We report two cases of patients with mantle cell lymphoma who relapsed after CAR T therapy and were treated with the bispecific CD20/CD3 T cell engaging antibody glofitamab. Both patients showed marked increases of circulating CAR T cells and objective responses after glofitamab administration. Therapy was tolerated without relevant side effects in both patients. One patient completed all 12 planned cycles of glofitamab therapy and was alive and without clinical progression at the last follow-up. The second patient declined further treatment after the first cycle and succumbed to disease progression. We review the literature and investigate possible mechanisms involved in the observed responses after administration of glofitamab, such as proliferation of CAR T cells, anti-tumor effects of the bispecific antibody and the role of other possibly contributing factors. Therapy with bispecific antibodies might offer an effective and well-tolerated option for patients with mantle cell lymphoma relapsing after CAR T therapy.

Accuracy of the functional, flow cytometer-based Emo-Test HIT Confirm® for the diagnosis of heparin-induced thrombocytopenia.

INTRODUCTION: Rapid functional assays have been proposed to overcome the limitations of washed platelet assays in the work-up of patients with suspected heparin-induced thrombocytopenia (HIT). Data on the diagnostic accuracy are, however, scarce and conflicting. We aimed to study the diagnostic accuracy of a rapid, flow cytometer-based assay and to explore sources of variability. MATERIAL AND METHODS: Frozen serum samples of 103 consecutive patients, evaluated for suspected HIT at our institution in 2017, and characterized with 4Ts score, IgG-PF4/heparin ELISA (GTI), HemosIL®Acustar (IgG), as well as heparin-induced platelet activation test (HIPA), were further tested using HIT Confirm, determining P-selectin release of donor platelets after incubation with patient's serum. The diagnosis of HIT was defined as a positive HIPA result. RESULTS: HIT was confirmed in 15 out of 103 patients corresponding to a prevalence of 14.6%. HIT Confirm was positive in 11 patients (10.7%), negative in 88 patients (85.4%), and inconclusive in 4 patients (3.9%). According to the intention-to-diagnose principle, the number of true positives was 9, the number of true negatives 83, the number of false negatives was 6, the number of false positives 5. This corresponds to a sensitivity of 60.0%, and a specificity of 94.3%. Modifications of the test did not improve sensitivity. CONCLUSIONS: The rapid, flow cytometer-based assay HIT Confirm is able to verify HIT in positive patient samples but cannot rule-out HIT in clinical practice. Other rapid functional assays shall be studies in appropriately designed diagnostic accuracy studies.