Real world data on outcomes of anti-CD38 antibody treated, including triple class refractory, patients with multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group (CMRG) Database.

Multiple myeloma (MM) remains incurable despite the availability of novel agents. This multi-center retrospective cohort study used the Canadian Myeloma Research Group Database to describe real-world outcomes of patients withanti-CD38 monoclonal antibody (mAb) refractory MM subsequently treated with standard of care (SoC) regimens. Patients with triple class refractory (TCR) disease (refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 mAb) were examined as a distinct cohort. Overall, 663 patients had disease progression on anti-CD38 mAb therapy, 466 received further treatment (346 with SoC regimens were included, 120 with investigational agents on clinical trial and were excluded). The median age at initiation of subsequent SoC therapy of 67.9 (range 39.6-89.6) years with a median of 3 prior lines (range 1-9). The median PFS and OS from the start of subsequent therapy was 4.6 (95% CI 4.1-5.6) months and 13.3 (95% CI 10.6-16.6) months, respectively. The median PFS and OS of patients with TCR disease (n = 199) was 4.4 (95% CI 3.6-5.3) months and 10.5 (95% CI 8.5-13.8) months. Our results reinforce that real-world patients with relapsed MM, particularly those with TCR disease, have dismal outcomes. There remains an urgent unmet need for the development of and access to effective therapeutics for these patients.

Management of chronic lymphocytic leukemia in Canada during the coronavirus pandemic.

The emergence of the covid-19 disease pandemic caused by the 2019 novel coronavirus has required a re-evaluation of treatment practices for clinicians caring for patients with chronic lymphocytic leukemia (cll). The American Society for Hematology (ash) has provided a series of recommendations for the treatment of patients with cll during the pandemic, covering a range of topics, including testing for covid-19, cll treatment initiation and selection, use of immunoglobulin therapy, in-person monitoring, and treatment of patients with cll and covid-19. We summarize the ash recommendations and discuss their applicability as guidelines for the treatment of cll during the covid-19 pandemic in Canada.

Synchrotron radiation analysis of possible correlations between metal status in human cementum and periodontal disease.

Periodontitis is a serious disease that affects up to 50% of an adult population. It is a chronic condition involving inflammation of the periodontal ligament and associated tissues leading to eventual tooth loss. Some evidence suggests that trace metals, especially zinc and copper, may be involved in the onset and severity of periodontitis. Thus we have used synchrotron X-ray fluorescence imaging on cross sections of diseased and healthy teeth using a microbeam to explore the distribution of trace metals in cementum and adhering plaque. The comparison between diseased and healthy teeth indicates that there are elevated levels of zinc, copper and nickel in diseased teeth as opposed to healthy teeth. This preliminary correlation between elevated levels of trace metals in the cementum and plaque of diseased teeth suggests that metals may play a role in the progress of periodontitis.

Utility of subsequent conventional dose chemotherapy in relapsed/refractory transplant-eligible patients with diffuse large B-cell lymphoma failing platinum-based salvage chemotherapy.

Up to 60% of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) do not respond to second-line (salvage) chemotherapy and hence are not offered autologous hematopoietic cell transplantation (AHCT). The utility of further salvage chemotherapy in an attempt to proceed with AHCT remains undefined. The authors reviewed 201 patients with DLBCL relapsed/refractory to anthracycline-based chemotherapy who received first-line salvage chemotherapy containing cis-platinum. Of the 120 non-responders to first-line platinum-based salvage chemotherapy, 73 received second-line salvage chemotherapy. The response rate to second-line salvage chemotherapy was 14%. Factors predicting lack of response were progression on primary therapy (p = 0.007), abnormal lactate dehydrogenase findings (p = 0.0027) and tumor bulk (p = 0.013) at second progression. Eight patients who responded received AHCT and appeared to have comparable survival to those transplanted after one salvage regimen. The authors conclude that the utility of second-line salvage chemotherapy is low, and that it is best reserved for patients demonstrating initial anthracycline sensitivity and low tumor burden.

G-CSF-stimulated BM progenitor cells supplement suboptimal peripheral blood hematopoietic progenitor cell collections for auto transplantation.

Peripheral blood hematopoietic progenitor cells (PBHC) are the standard source of support for high-dose chemotherapy because of faster recovery of marrow function. Unfortunately, a proportion of patients are unable to mobilize adequate progenitors to proceed to autologous hematopoietic cell transplant (AHCT). Granulocyte-CSF-stimulated BM-derived hematopoietic progenitor cells (BMHC) may circumvent this problem. From 1999 to 2006, 52 patients (cases) with AML, Hodgkin (HL) or non-Hodgkin's lymphoma (NHL) in whom PBHC mobilization failed underwent a G-CSF-stimulated bone marrow harvest and proceeded to AHCT. Their outcome was compared with 422 patients (controls) with AML, HL and NHL undergoing AHCT using only PBHC. Twenty-three patients received BMHC alone and 29 patients received a combination of PBHC and BMHC. Median engraftment time for neutrophils (>0.5 x 10(9)/l) and platelets (>20 x 10(9)/l) were 14 and 27 days, but significantly longer when compared with controls (11 days, 11 days, P<0.0001). Patients receiving both PBHC and BMHC had faster engraftment, when compared with those receiving BMHC alone (P<0.001). In conclusion, performing an AHCT using G-CSF-stimulated BMHC in patients failing PBHC collection is feasible with faster engraftment seen in patients receiving both BMHC and PBHC over BMHC alone.

Evidence of graft-versus-Waldenstrom's macroglobulinaemia effect after allogeneic stem cell transplantation: a single centre experience.

The role of allogeneic stem cell transplantation (SCT) in Waldenstrom's macroglobulinaemia (WM) is not yet clear, as published data on allogeneic SCT in WM are limited. We present a retrospective study of allogeneic SCT in five patients with WM. Median age was 56 years (range 40-60 years). All patients were heavily pretreated. Conditioning therapy with busulphan and cyclophosphamide was used for all patients and all were given cyclosporine and methotrexate for graft-versus-host disease prophylaxis. With a median follow-up of 32 months (range 2-43), all except one are alive and disease free. Progressive, delayed decline in serum IgM levels were noted in all the patients, suggesting an active graft-versus-Waldenstrom's effect. With the limited available data, it appears that allogeneic SCT is a useful treatment option for advanced WM.