A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial.

We conducted a randomized, controlled trial comparing thalidomide-prednisone as maintenance therapy with observation in 332 patients who had undergone autologous stem cell transplantation with melphalan 200 mg/m2. The primary end point was overall survival (OS); secondary end points were myeloma-specific progression-free survival,progression-free survival, incidence of venous thromboembolism, and health-related quality of life (HRQoL). With a median follow-up of 4.1 years, no differences in OS between thalidomide-prednisone and observation were detected (respective 4-year estimates of 68% vs 60%, respectively; hazard ratio = 0.77; P = .18); thalidomide-prednisone was associated with superior myeloma-specific progression-free survival and progression-free survival (for both outcomes, the 4-year estimates were 32% vs 14%; hazard ratio = 0.56; P < .0001) and more frequent venous thromboembolism (7.3% vs none; P = .0004). Median survival after first disease recurrence was 27.7 months with thalidomide-prednisone and 34.1 months in the observation group. Nine second malignancies were observed with thalidomide-prednisone versus 6 in the observation group. Those allocated to thalidomide-prednisone reported worse HRQoL with respect to cognitive function, dyspnea, constipation, thirst, leg swelling, numbness, dry mouth, and balance problems. We conclude that maintenance therapy with thalidomide-prednisone after autologous stem cell transplantation improves the duration of disease control, but is associated with worsening of patient-reported HRQoL and no detectable OS benefit.

Comparison of serious adverse events between the original and a generic docetaxel in breast cancer patients.

BACKGROUND: Generic formulations are not necessarily identical to the original in terms of efficacy and adverse events. Generic docetaxel has been available in Canada since 2011. OBJECTIVE: To compare the occurrence of grade III to IV adverse events between original docetaxel and a generic formulation in breast cancer patients. METHODS: A consecutive series of 400 patients were assessed retrospectively: 200 who received the original docetaxel and 200 who received a generic formulation. Patients who received both formulations or received their chemotherapy outside our center were excluded. The primary outcome was the occurrence of grade III to IV adverse events related to docetaxel (febrile neutropenia, hand and foot syndrome, intestinal perforation, thrombotic event, and death). RESULTS: Three hundred-sixty-four patients were available for analysis (182/group). The use of a granulocyte colony-stimulating factor (G-CSF) was more frequent in the generic group (44.5% vs 28.8%), as well as treatment discontinuation (26.4% vs 14.8%). The occurrence of grade III to IV febrile neutropenia, hand and foot syndrome, intestinal perforation, thrombotic event, and docetaxel-related deaths were similar between the 2 formulations. However, grade IV febrile neutropenia was more frequent with the generic formulation (78.8% vs 56.3%). Limitations were the retrospective nature of the study and the variety of chemotherapy regimens. CONCLUSION: Adverse events occurrence was similar between the 2 formulations. However, febrile neutropenia was more serious with generic docetaxel, despite increased G-CSF use. Results suggest that the studied generic formulation may be safe, but more caution during treatments might be warranted, especially concerning febrile neutropenia events.

Management of Oligometastatic Breast Cancer: An Expert Committee's Opinion.

Patients with oligometastatic breast cancer (BC) are candidates of choice for metastasis-directed therapy (MDT). This paper summarizes the opinions of an expert committee about the management of oligometastatic BC. The experts could complete the questionnaire from 13 September 2021, to 10 October 2021, followed by a discussion. The experts were physicians working in the Province of Quebec (Canada) and specialized in BC care, including surgical oncologists, medical oncologists, and radiation oncologists. The experts provided their opinions about the context of the disease and therapeutic approach, local and systemic therapies, and the prognosis of oligometastatic BC. In addition to the expert panel's opinions about the management of oligometastatic disease per se, the experts stated that a prospective data registry should be implemented to collect data about oligometastatic BC to improve knowledge about oligometastatic BC and implement data-driven MDT. These data could also allow for the design of treatment algorithms. In conclusion, this paper presents the expert panel's opinions about the management of oligometastatic BC and highlights the needs to be met to improve the care of this condition.

Abstracts of the Cell Therapy Transplant Canada 2022 Annual Conference.

On behalf of Cell Therapy Transplant Canada (CTTC), we are pleased to present the Abstracts of the CTTC 2022 Annual Conference. The conference was held in-person 15-18 June 2022, in Niagara Falls, Ontario. Poster authors presented their work during a lively and engaging welcome reception on Thursday, 16 June, and oral abstract authors were featured during the oral abstract session in the afternoon on Friday, 17 June 2022. Thirty-three (33) abstracts were selected for presentation as posters and six (6) as oral presentations. The top abstracts in each of four (4) categories, (1) Basic/Translational sciences, (2) Clinical Trials/Observations, (3) Laboratory/Quality, and (4) Pharmacy/Nursing/Other Transplant Support, received awards for both the oral and poster presentations. All of these were marked as "Award Recipient" with the relevant category. We congratulate all the presenters on their research and contribution to the field.

Obinutuzumab plus fludarabine and cyclophosphamide in previously untreated, fit patients with chronic lymphocytic leukemia: a subgroup analysis of the GREEN study.

GREEN (NCT01905943) is a nonrandomized, open-label, single-arm, phase 3b study investigating the safety and efficacy of obinutuzumab alone or in combination with chemotherapy in chronic lymphocytic leukemia (CLL). We report the preplanned subgroup analysis of 140 previously untreated, fit CLL patients who received obinutuzumab plus fludarabine and cyclophosphamide (G-FC). The primary endpoint was safety and tolerability. Efficacy was the secondary endpoint. Obinutuzumab 1000 mg was administered intravenously on Day (D)1 (dose split D1‒2), D8 and D15 of Cycle (C)1, and D1 of C2-6 (28-day cycles). Standard intravenous/oral doses of fludarabine and cyclophosphamide were administered on D1-3 of C1-6. Overall, 87.1% of patients experienced grade ≥ 3 adverse events (AEs), including neutropenia (67.1%) and thrombocytopenia (17.1%). Serious AEs were experienced by 42.1% of patients. Rates of grade ≥ 3 infusion-related reactions and infections were 19.3% and 15.7%, respectively. Overall response rate was observed in 90.0%, with 46.4% of patients achieving complete response (CR; including CR with incomplete marrow recovery). Minimal residual disease negativity rates were 64.3% in peripheral blood and 35.7% in bone marrow (intent-to-treat analysis). After a median observation time of 25.6 months, 2 year progression-free survival was 91%. Frontline G-FC represents a promising treatment option for fit patients with CLL.

A voluntary conservation agreement reduces the risks of lethal collisions between ships and whales in the St. Lawrence Estuary (Québec, Canada): From co-construction to monitoring compliance and assessing effectiveness.

Lethal collisions with ships are limiting the recovery of several at-risk whale species worldwide. In the St. Lawrence Estuary (Quebec, Canada), the endangered blue whale and of special concern fin whale are among the migratory species subject to collisions with large ships. In 2011, a working group composed of representatives from the maritime industry, the government, non-governmental organizations, and academia was created to explore solutions to mitigate ship-whale collisions in the St. Lawrence Estuary. Adopting an adaptive risk management framework, the working group took advantage of the best available scientific data and tools to co-construct realistic collision mitigation options and evaluate their likely benefits for whale conservation and costs for the industry. In 2013, the working group recommended the implementation of voluntary measures to mitigate collision risks, consisting of a slow-down area, a no-go area, and a caution area; a recommended route was added in 2014. Along with the voluntary framework, the working group agreed to continuously monitor compliance with and assess effectiveness of these mitigation measures. After the fourth year of implementation, voluntary measures showed encouraging results, with a reduction of up to 40% of lethal collision risks with fin whales in the highest density area. This reduction in risk is mainly related to ship speed reduction in the slow-down area from 14.1 ± 2.6 knots in 2012 to 11.3 ± 1.7 knots since 2014. The presence of a mandatory pilotage area overlapping with the slow-down area was instrumental to facilitate communication about the mitigation measures, with the pilotage corporation sitting as a regular member of the working group. This resulted in significantly slower speeds in the slow-down area for ships with a pilot from the pilotage corporation onboard compared to those without (-0.8 knots, p-value < 0.001). It is also likely to explain the weaker compliance of the maritime industry with the no-go area located outside of the mandatory pilotage area. Other factors of success include: the continuous dedication of the government to a voluntary and transparent participatory process; the use of available data, tools and institutions; the presence of an environmental certification program representative in the working group; and the adoption by consensus of an adaptive risk management approach. The traditional regulatory approach to conservation is often blamed for its focus on deterring negative behaviors, doing nothing to encourage and reward positive ones. In agreement with other case studies, the benefits of the voluntary measures implemented in the St. Lawrence Estuary include the pro-active commitment from the industry (which is likely to reduce conflicts with regulators), the greater flexibility and freedom that allowed to come up with cost-effective and tailored-made mitigation measures, and the fast achievement of conservation gains. More importantly perhaps, the human and working capital built throughout the concertation process have the potential to be a fundamental cornerstone in dealing with more complex issues such as the chronically increasing level of underwater noise in whale habitats.

Evaluation of eligibility and recruitment in breast cancer clinical trials.

Objectives of the study were to measure recruitment rates in clinical trials and to identify patients, physicians or trials characteristics associated with higher recruitment rates. Among patients who had a clinical trial available for their cancer, 83.5% (345/413) met the eligibility criteria to at least one clinical trial. At least one trial was proposed to 33.1% (113/341) of the eligible patients and 19.7% (68/345) were recruited. Overall recruitment was 16.5% (68/413). In multivariate analyses, trial proposal and enrollment were lower for elderly patients and higher in high cancer stages. Trials from pharmaceutical industry had higher recruitment rates and trials testing hormonal therapy enrolled more patients. Breast cancer patients' accrual to a clinical trial could be improved by trying to systematically identify all eligible patients and propose a trial to those eligible and to whom the treatment is planned to be equivalent to the standard arm of the trial.

Bortezomib ADDED to R-CVP is safe and effective for previously untreated advanced-stage follicular lymphoma: a phase II study by the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Bortezomib has demonstrated promising activity in patients with follicular lymphoma (FL). This is the first study to evaluate the safety and efficacy of bortezomib added to rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) in previously untreated advanced-stage FL. PATIENTS AND METHODS: This is a phase II multicenter trial adding bortezomib (1.3 mg/m(2) days 1 and 8) to standard-dose R-CVP (BR-CVP) for up to eight cycles in patients with newly diagnosed stage III/IV FL requiring therapy. Two co-primary end points, complete response rate (complete response [CR]/CR unconfirmed [CRu]) and incidence of grade 3 or 4 neurotoxicity, were assessed. RESULTS: Between December 2006 and March 2009, 94 patients were treated with BR-CVP. Median patient age was 57 years (range, 29 to 84 years), and the majority had a high (47%) or intermediate (43%) Follicular Lymphoma International Prognostic Index score. BR-CVP was extremely well tolerated, with 90% of patients completing the intended eight cycles. No patients developed grade 4 neurotoxicity, and only five of 94 patients (5%; 95% CI, 0.8% to 9.9%) developed grade 3 neurotoxicity, which was largely reversible. On the basis of an intention-to-treat analysis, 46 of 94 patients (49%; 95% CI, 38.8% to 59.0%) achieved a CR/CRu, and 32 of 94 patients (34%) achieved a partial response, for an overall response rate of 83% (95% CI, 75.4% to 90.6%). CONCLUSION: The addition of bortezomib to standard-dose R-CVP for advanced-stage FL is feasible and well tolerated with minimal additional toxicity. The complete response rate in this high-risk population compares favorably to historical results of patients receiving R-CVP. Given these results, a phase III trial comparing BR-CVP with R-CVP is planned.

Canadian multicenter pilot trial of haploidentical donor transplantation.

BACKGROUND: Canadian multicenter pilot study of haploidentical donor. AIMS: To assess (1) ability to collect suitable graft (CD34+ > or = 5 x 10(6)/kg and CD3 < 1 x 10(5)/kg recipient body weight), (2) toxicity, (3) survival to day +100. ELIGIBILITY: All hematological malignancies and ages; accrual to end after 20 transplants of patients with AML in remission and age less than 55 years. METHODS: Preparation: Modified Perugia regimen, chemotherapy alone; melphalan 140 mg/m2 day -9, thiotepa 10 mg/kg day -7, fludarabine 40 mg/m2 days -7 to -3, and ATG (Thymoglobulin, Sangstat) days -6 to -2 (total 10.5 mg/kg). Infection prophylaxis: Ganciclovir (GC) 5 mg/kg days 5-20 then x5/week until day +100 then x3/week until 210 (subjects 1-3), foscarnet (FC) 90 mg/kg days 4-21 then short course pre-emptive GC or FC (subjects 4-11); fluconazole; cotrimoxazole. Donors: G-CSF 16 microg/kg daily x5 until second pheresis day. T-cell depletion: CliniMACS (MiltenyiBiotec). RESULTS: Eleven patients with AML have been transplanted from four centers, eight female, three male, median age 34 (range 19-60). Disease status, first CR 1/11, second CR 4/11, third CR1/11, relapse 5/11. Graft CD34+ > or = 5 x 10(6)/kg was achieved in all cases, median 13.72 x 10(6)/kg (Q1, Q3: 8.26, 17.72; min 5.59, max 22.22), and CD3+ was < 1 x 10(5)/kg in all cases, median of 0.49 x 10(4)/kg (Q1, Q3: 0.30, 2.20; min 0.22, max 4.10). Ten of the 11 patients have died, median survival 103.5 days (Q1, Q3: 61.0, 151.0; min 0, max 290.0). Survival to day +100 6/11 (55%). Four patients died of leukemic relapse, six of infection. Of six patients dying of infection, CMV was a definite cause in four. Of four dying with relapse, CMV was significant in one. Engraftment was assessed in 10 patients who survived >0 days. Granulocyte engraftment (> 0.5 x 10(9)/l) was achieved in all patients, median 11.5 days (Q1, Q3: 10, 17; min 8, max 70). Platelet engraftment (> 20 x 10(9)/l) was achieved in 8 of 10 patients, median 15 days (Q1, Q3: 9, 16; min 9, max 97). The two platelet non-engrafters died on days +45 and +61. Toxicity was low, with one toxic death (day 0), and the Bearman organ toxicity gradings were < or = grade 2 in all other patients. There were no instances of graft-vs.-host disease or graft rejection. CONCLUSIONS: The problems of graft-vs.-host disease and graft rejection have been removed as barriers to haploidentical transplantation but the slow immune reconstitution limits its general application. Late referrals contribute to a high relapse rate and have delayed an optimal evaluation of the procedure.