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Interim imaging with computed tomography (iCT) to assess response is common during frontline chemoimmunotherapy for follicular lymphoma (FL), but there is little evidence of its utility. We retrospectively reviewed outcomes of iCT in 190 patients with biopsy-proven FL who received first-line chemoimmunotherapy from 2003-2018. Most iCTs showed partial response (PR, 83%), with a minority showing complete response (CR, 8%) or stable disease (5%). Seven patients (4%) had radiographic disease progression (PD) on iCT; on repeat biopsy, four had another malignancy identified and three had transformation to DLBCL. Only one had asymptomatic PD. The 3-year PFS of all patients was 74% (median follow up 75 months). Patients with PR on iCT had similar 3-year PFS and OS as those with CR. In conclusion, iCT has limited utility in identifying patients with asymptomatic early progression during first-line treatment. Patients with PD mid-treatment warrant biopsy to identify histologic transformation or other malignancies.

Lenalidomide is a backbone agent in the treatment of multiple myeloma, but dose adjustment is required for those with renal impairment (RI). We evaluated the pharmacokinetics (PK) and safety of lenalidomide and dexamethasone as frontline pre-transplant induction, with doses adjusted at start of each cycle based on creatinine clearance, as per the official dosing guidelines. After 4 cycles, PK studies showed that patients with moderate RI (30 ≤ CrCl < 60 mL/min) receiving 10 mg dosing may be under-dosed and those with severe RI (CrCl <30ml/min) appeared appropriately dosed initially, but sustained significant decreases in maximum serum concentration (Cmax) after repeated dosing, due to rapid clinical improvement and enhanced drug clearance. PK drug monitoring during cycle 1 may facilitate appropriate and timely dose adjustments. Adverse events rates did not vary based on severity of RI. No patient discontinued lenalidomide for toxicity. This supports the feasibility and safety of frontline lenalidomide in transplant-eligible patients with RI.

Bleomycin pulmonary toxicity (BPT) is a well-described complication of bleomycin-containing regimens. Previous data on risk factors and the impact of BPT on survival in Hodgkin lymphoma (HL) were conflicting. We reviewed 253 HL patients treated with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) at the Princess Margaret Hospital from 1999 to 2009 to examine the incidence and risk factors for BPT, and the effect of BPT on survival. BPT was defined by pulmonary symptoms, bilateral interstitial infiltrates on computed tomography, and the absence of infection. Kaplan-Meier estimates were used to compare overall survival (OS) and progression-free survival (PFS) between groups. The incidence of BPT was low (11%). Age ≥45 (OR = 2.5) and granulocyte colony-stimulating factor use (OR = 3.6) were identified as predictors of BPT on multivariable logistic models. At a follow-up of 5 years, OS and PFS were 88% and 82%, respectively. Neither BPT nor bleomycin discontinuation had significant impact on survival outcomes.

Rituximab is a monoclonal anti-CD20 antibody that is standard of care for treatment of B-cell non-Hodgkin lymphoma (NHL). The purpose of this study was to quantify the incidence of rituximab (R)-related interstitial pneumonitis (IP) in patients with NHL receiving immunochemotherapy. All patients with NHL who received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), cyclophosphamide, vincristine and prednisone (CVP), R-CHOP or R-CVP in Princess Margaret Hospital between June 1998 and August 2009 were retrospectively reviewed. We compared cohorts of patients who did and did not receive R and documented the incidence of IP during and/or post-treatment. In total 560 patients were included in this analysis. The rate of IP in the entire cohort was 2.9% (16/560) with a trend toward a higher rate in the R group (3.95% vs. 1.3% [odds ratio 3.1, 0.84-17.27, p = 0.074]). Baseline pulmonary computed tomography abnormalities in patients with lymphoma are relatively common. The addition of R to chemotherapy does not significantly increase the risk of symptomatic chemotherapy-related IP.

Neutropenia is a major dose-limiting toxicity associated with lenalidomide in relapsed/refractory multiple myeloma (MM). The optimal dosing schedule of granulocyte colony-stimulating factor (G-CSF) is unclear. We developed an intermittent G-CSF schedule (4-6 doses per cycle) initiated upon onset of grade 3-4 neutropenia. Of 216 patients with relapsed/refractory MM treated at our center with lenalidomide/dexamethasone on an Expanded Access Program, there was a high incidence of grade 3-4 neutropenia (61%) and grade 3-4 infections (37%). Despite intermittent G-CSF use in 117 patients, recurrent grade 3-4 neutropenia was common (59%), and dose reductions were required in 40% of G-CSF recipients, most due to thrombocytopenia. G-CSF recipients had a longer duration on therapy and achieved a higher rate and depth of response. Intermittent G-CSF may be an effective approach for lenalidomide dose-preservation, which may lead to improved outcomes, although it does not prevent infections or thrombocytopenia-related dose limitations.

Post-autologous stem cell transplant (ASCT) studies have demonstrated that absolute lymphocyte count (ALC) recovery is associated with prolonged survival in some hematological malignancies. To assess whether ALC recovery has prognostic significance in patients with multiple myeloma (MM) undergoing single ASCT, we conducted a retrospective analysis of ALC at different time-points in patients with MM. In total 769 consecutive patients who underwent single ASCT from January 2000 to December 2007 were evaluated. An ALC of ≥ 1400 cells/μL at day 0, day 15 and day 90 significantly correlated with a better overall survival (OS) (median OS of 111, 90.7 and 84 months vs. 74, 70.5 and 65 months, respectively, p < 0.001 for all time-points). Multivariate analysis showed that ALC is an independent prognostic factor for OS after ASCT. In conclusion, ALC is a surrogate marker of the host immune system that correlates with better survival in patients with MM undergoing single ASCT. Immunomodulatory drugs, vaccination strategies and cellular therapies in MM should be investigated.

Follicular lymphoma (FL) is characterized by an initial response to treatment with inevitable relapse. We evaluated chemoimmunotherapy resistance (CIR resistance) including transformation. We identified patients who received rituximab combination therapy for symptomatic FL. CIR resistance was defined as disease progression during rituximab-based chemoimmunotherapy, rituximab maintenance or within 6 months of treatment completion. Our primary outcome was time to early progression (CIR resistance). Between July 2006 and April 2010, 132 patients met the inclusion criteria and 22 (16.7%) demonstrated CIR resistance with a median follow-up of 33 months. High-risk Follicular Lymphoma International Prognostic Index (FLIPI) score was predictive of CIR resistance (hazard ratio [HR] 2.43; 95% confidence interval [CI], 1.4-4.1; p = 0.001). Overall, eight patients (36.3%) transformed (biopsy-proven), with no transformation in the chemoimmunotherapy responder group. Median overall survival in the CIR resistant group was 47 months. Patients with CIR resistance had high rates of histologic transformation and shorter survival with poor response to next therapy.

Abstract Recently, the occurrence of oligoclonal and monoclonal bands (OB/MB) unrelated to the original clone has been reported in patients with multiple myeloma who undergo autologous stem cell transplant (ASCT) and/or receive treatment with novel agents. The aim of our study was to assess the impact of OB/MB occurrence on overall (OS) and progression-free survival (PFS) for patients with MM undergoing single ASCT at our institution. All consecutive patients with documented MM undergoing single ASCT from January 2000 to December 2012 were evaluated. Ninety-nine patients (11.8%) developed OB/MB at day 100 post-ASCT (32.3%, OB and 67.7%, MB). Multivariate analysis identified the development of OBs/MBs as an independent favorable prognostic factor for OS and PFS (p = 0.008 and 0.012, respectively). In conclusion, the occurrence of OB/MB is an important prognostic factor in patients with MM who undergo ASCT. Its impact on clinical outcomes should be prospectively validated and its biological significance further elucidated.

This is a randomized trial evaluating the safety and immunogenicity of one or two doses of 2009 pandemic H1N1 influenza vaccination in adults with lymphoid malignancies. Adults with a lymphoid malignancy receiving active systemic therapy, or within a year after autologous stem cell transplant, received one dose of AS03-adjuvanted A/California/7/2009 (H1N1) vaccine, and were randomized 21 days later to a second dose or no further vaccination. The primary outcomes were seroprotection and seroconversion rates by hemagglutination inhibition 21 and 42 days after initial vaccination. Twenty-two patients received one dose, and 20 patients received a second dose. Seroconversion rates at day 21 were 30% (one dose) and 5% (two doses), and subsequently 30% for both groups at day 42. Seroprotection rates at day 21 were 40% (one dose) and 15% (two doses), and subsequently 35% (one dose) and 40% (two doses) at day 42. Differences in serologic endpoints were not statistically significant between both study arms at day 42. Patients with low levels of B-cells (CD19-positive) had low seroconversion rates on days 21 (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.59-0.93, p = 0.043) and 42 (OR 0.12, 95% CI 0.01-1.07, p = 0.058). Only three of the 14 patients who received rituximab achieved seroprotective titers by day 42. Patients with lymphoid malignancies did not achieve rates of seroconversion or seroprotection seen in healthy subjects despite a second dose and the use of an adjuvant. Notwithstanding suboptimal immunogenicity, seasonal and pandemic influenza vaccination should continue to be recommended.

The combination of lenalidomide, bortezomib and dexamethasone (RVD) has shown excellent efficacy in patients with relapsed or refractory multiple myeloma (RRMM). The aim of our study was to assess the efficacy and toxicity profile of RVD for patients with advanced RRMM. We retrospectively reviewed the records of all patients with RRMM treated with RVD between March 2009 and December 2011. Thirty patients received ≥ 1 full cycle of RVD. Primary endpoints were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). After a median of 5 cycles (1-16), a very good partial response (VGPR) was seen in 10%, partial response (PR) in 36.7% and stable disease (SD) in 13.3% (ORR of 46.7%). Disease progression occurred in 21 patients at a median of 3 months (range 1.41-4.59). Eight patients (26%) experienced grade 3/4 adverse events, including anemia, neutropenia, muscle weakness and pneumonia. No patient experienced worsening peripheral neuropathy. Although RVD has been previously shown to be effective in RRMM, the ORR and PFS we observed were affected by very advanced disease status and heavy prior exposure to novel agents. Nevertheless, six of these patients with RRMM experienced a benefit of ≥ 6 months, suggesting synergism of this immunomodulatory derivative/proteasome inhibitor combination and/or re-establishment of drug sensitivity by an emergent myeloma clone.

Mantle-cell lymphoma (MCL) is a rare cancer, with the majority of patients (pts) presenting in stage III-IV and the outcomes are poor. To determine the curability of localized MCL, we examine stage I-II pts at our institution between 1990-2007. 26 pts with stage I (38%) and stage II (62%) were referred. Sites involved were head and neck in 73%. Five had a blastoid variant. Five patients were treated with palliative intent. Analysis was focused on pts treated with a curative intent (21 pts): 17 CT+RT, 2 RT, 2 CT followed by ASCT. 13 patients received CHOP, 5-RCHOP, 1-CVP; most received 6 cycles. The RT median dose was 35Gy and IFRT for the majority. For 21 pts treated with a curative intent, median follow up was 5.8 years. The overall response rate was 95%. Among the 19 CR/CRu pts, 9 relapsed for a 5-year relapse rate of 46%. Relapses were mainly observed at distant sites, 3 were in GI tract, 1 had both local and distant relapse. Median PFS and OS were 3.2 and 6.4 years, respectively. 5-year OS was 62%. In univariate analysis, blastoid variant and stage II were prognostic factors for PFS. Multivariate analysis could not be performed due to the small sample size. With a treatment approach using combined CT+RT for stage I-II MCL, local control was achieved in 94%. Systemic relapse remains a significant problem, especially for stage II and blastoid variant. Radiotherapy should remain part of curative treatment plan in stage I-II MCL.