Undetectable peripheral blood MRD should be the goal of venetoclax in CLL, but attainment plateaus after 24 months.

The highly selective BCL2 inhibitor venetoclax achieves deep responses in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL), including undetectable minimal residual disease (uMRD). We retrospectively reviewed 62 patients with CLL treated with venetoclax to investigate the performance of peripheral blood (PB) compared with bone marrow (BM) assessment of MRD; the kinetics, clinicopathological associations, and longer-term outcomes of uMRD attainment and recrudescence; and the ability of venetoclax dose escalation to deepen responses. Among 16 patients who achieved PB uMRD and had contemporaneous BM assessments, 13 (81%) had confirmed BM uMRD, and patients with PB uMRD had outcomes at least as favorable as those with BM uMRD for time to progression, overall survival, and MRD recrudescence. Excluding 2 patients lacking earlier assessment, the median time to PB uMRD was 18 (range, 5-26) months, with 90% of instances achieved by 24 months. There was no new PB uMRD attainment after 24 months without treatment intensification. The dominant association with earlier attainment of uMRD was concurrent rituximab (P = .012). Complex karyotype was associated with inferior uMRD attainment after 12 months of therapy (P = .015), and patients attaining uMRD whose disease harbored TP53 abnormalities demonstrated a trend toward earlier recrudescence (P = .089). Of patients who received venetoclax dose escalations, 4 (27%) of 15 achieved improvements in response. For patients with R/R CLL receiving venetoclax, PB uMRD commonly correlates with BM uMRD and is associated with a comparable longer-term prognosis. Concurrent rituximab augments uMRD attainment, but dose escalation and further treatment beyond 24 months infrequently deepen responses.

Bone-marrow plasma cell burden correlates with IgM paraprotein concentration in Waldenstrom macroglobulinaemia.

AIMS: Correlations between the marrow histopathology and clinical findings in Waldenström macroglobulinaemia (WM) are not well defined, and the pathophysiology of the plasma cell involvement is poorly understood. The authors used a standardised immunohistological approach to the enumeration of B lymphocyte and plasma cell compartments in the bone-marrow trephine to investigate associations between bone-marrow morphology and clinical/laboratory indices. METHODS: In 80 newly diagnosed, untreated cases of WM, the authors determined the degree and pattern of B lymphocyte (CD20+) and plasma cell (CD138+) infiltration in the bone-marrow trephine, as defined by immunohistochemistry, and correlated the disease in the marrow with components of the international scoring system for WM (age, serum IgM paraprotein level, haemoglobin, platelet count and ß(2) microglobulin). Plasma cell clonality was assessed by κ and λ staining. RESULTS: Serum IgM paraprotein concentration was related to the plasma cell burden in the bone marrow (coefficient 0.231, p<0.005), but not the B lymphocytic infiltrate. Overall lymphoplasmacytic disease burden weakly correlated with severity of anaemia (coefficient 0.236, p=0.055). In 28/28 evaluated cases, plasma cells exhibited light chain restriction that was concordant with both that of the B lymphocytic infiltrate and paraprotein. CONCLUSIONS: Bone-marrow features, in particular the degree of plasma cell infiltration, correlate with IgM paraprotein concentration at diagnosis in WM. The plasma cell compartment in this condition appears to be part of the neoplastic clone. In WM, specific evaluation of the plasma cell compartment in the bone marrow at baseline and following therapy may be valuable.