This study compared the quality-adjusted effectiveness and costs of three treatment options for transplant-eligible patients with early progression (POD24) of follicular lymphoma. A Markov ...decision-analytic model using a 20-year time horizon was used to compare allogeneic stem cell transplant (alloSCT), autologous stem cell transplant (ASCT), and chemo-immunotherapy (O-CHOP). For second relapse/refractory disease, novel therapy use was modeled, including lenalidomide and rituximab/obinutuzumab, and PI3K inhibitors (PI3Ki). Costs were considered from a Canadian public health payer's perspective. Probabilistic analyses (10,000 simulations) demonstrated that at a willingness-to-pay threshold of $50,000, ASCT was most cost effective 60% of the time. ASCT resulted in more life years (10.2 vs. alloSCT 9.9 vs. O-CHOP 10.0) and quality-adjusted life years (7.5 vs. alloSCT 6.6 vs. O-CHOP 7.4), with the lowest direct costs ($190,128 CAD). In sensitivity analyses, the model was robust to key variables, including differing probabilities of progression, non-relapse mortality, graft-versus-host-disease (GVHD), costs of treating GVHD, costs of PI3Ki, and probability of secondary malignancy from ASCT. However, if patients were older than 65 years or their life expectancy was less than 10 years, chemo-immunotherapy was the preferred strategy. When considering cost, effectiveness, and toxicities, the preferred treatment strategy for most patients with POD24 follicular lymphoma is ASCT.
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The objective of this study was to perform a systematic review of the literature on vaccine responsiveness in patients who have received anti-CD20 therapy. PubMed and EMBASE were ...searched up to 4 January 2021 to identify studies of vaccine immunogenicity in patients treated with anti-CD20 therapy, including patients with hematologic malignancy or autoimmune disease. The primary outcomes were seroprotection (SP), seroconversion (SC), and/or seroresponse rates for each type of vaccine reported. As the pandemic influenza vaccine (2009 H1N1) has standardized definitions for SP and SC, and represented a novel primary antigen similar to the COVID-19 vaccine, meta-analysis was conducted for SC of studies of this vaccine. Pooled estimates, relative benefit ratios (RBs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-eight studies (905 patients treated with anti-CD20 therapy) were included (19 studies of patients with hematologic malignancies). Patients on active (<3 months since last dose) anti-CD20 therapy had poor responses to all types of vaccines. The pooled estimate for SC after 1 pandemic influenza vaccine dose in these patients was 3% (95% CI, 0% to 9%), with an RB of 0.05 (95% CI, 0-0.73) compared with healthy controls and 0.22 (95% CI, 0.09-0.56) compared with disease controls. SC compared with controls seems abrogated for at least 6 months following treatment (3-6 months post anti-CD20 therapy with an RB of 0.50 95% CI, 0.24-1.06 compared with healthy and of 0.44 95% CI, 0.23-0.84 compared with disease controls). For all vaccine types, response to vaccination improves incrementally over time, but may not reach the level of healthy controls even 12 months after therapy.
There is increasing interest from cancer patients and their healthcare providers in the use of virtual care in routine clinical practice. In the setting of hematologic malignancy, where patients ...often undergo complex and immunodepleting treatments, understanding how to use virtual care safely and effectively is critically important. We aimed to describe the use of virtual care in patients with hematologic malignancies and to examine physician- and patient-reported outcomes in the form of a systematic scoping review. An electronic search of PubMed, Ovid MEDLINE, Elsevier Embase, Scopus, and EBSCO CINAHL was conducted from January 2000 to April 2021. A comprehensive search strategy was used to identify relevant articles, and data were extracted to assess the study design, population, setting, patient characteristics, virtual care platform, and study results. Studies were included if they described the use of virtual care for patients with hematologic malignancies; commentaries were excluded. Fifteen studies met the inclusion criteria after abstract and full-text review. Three studies found that app-based tools were effective in monitoring patient symptoms and triggering alerts for more urgent follow-up. Four studies described the use of phone-based interventions. Five studies found that videoconferencing, with both physicians and oncology nurses, was highly rated by patients. Emerging themes included high levels of patient satisfaction across all domains of virtual care. Provider satisfaction scores were rated lower than patient scores, with concerns about technical issues leading to challenges with virtual care. Four studies found that virtual care allowed providers to promptly respond to patient concerns, especially when patients were experiencing side-effects or had questions about their treatment. Overall, the use of virtual care in patients with hematologic malignancies appears feasible, and resulted in high patient satisfaction. Further research is needed in order to evaluate the optimal method of integrating virtual care into clinical practice.
Recent studies of polatuzumab vedotin and CD19 chimeric antigen receptor T-cell therapy (CAR-T) have shown significant improvements in progression-free survival over standard of care (SOC) for ...patients with diffuse large B-cell lymphoma. However, they are costly, and it is unclear whether these strategies, alone or combined, are cost-effective over SOC.
A Markov model was constructed to compare four strategies for patients with newly diagnosed intermediate- to high-risk diffuse large B-cell lymphoma: strategy 1: polatuzumab-rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) plus second-line CAR-T for early relapse (< 12 months); strategy 2: polatuzumab-R-CHP plus second-line salvage therapy ± autologous stem-cell transplant; strategy 3: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone plus second-line CAR-T for early relapse; strategy 4: SOC (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone plus second-line salvage therapy ± autologous stem-cell transplant). Transition probabilities were estimated from trial data. Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated from US and Canadian payer perspectives. Willingness-to-pay (WTP) thresholds of $150,000 US dollars (USD) or Canadian dollars (CAD)/QALY were used.
In probabilistic analyses (10,000 simulations), each strategy was incrementally more effective than the previous strategy, but also more costly. Adding polatuzumab-R-CHP to the SOC had an ICER of $546,956 (338,797-1,199,923) USD/QALY and $245,381 (151,671-573,250) CAD/QALY. Adding second-line CAR-T to the SOC had an ICER of $309,813 (190,197-694,200) USD/QALY and $303,163 (221,300-1,063,864) CAD/QALY. Simultaneously adding both polatuzumab-R-CHP and second-line CAR-T to the SOC had an ICER of $488,284 (326,765-840,157) USD/QALY and $267,050 (182,832-520,922) CAD/QALY.
Given uncertain incremental benefits in long-term survival and high costs, neither polatuzumab-R-CHP frontline, CAR-T second-line, nor a combination are likely to be cost-effective in the United States or Canada at current pricing compared with the SOC.
Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the ...risk of death and other important outcomes for these patients. We searched PubMed and EMBASE up to 20 August 2020 to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of intensive care unit admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-four adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14 of 34 adult studies included only hospitalized patients). Risk of death among adult patients was 34% (95% CI, 28-39; N = 3240) in this sample of predominantly hospitalized patients. Patients aged ≥60 years had a significantly higher risk of death than patients <60 years (RR, 1.82; 95% CI, 1.45-2.27; N = 1169). The risk of death in pediatric patients was 4% (95% CI, 1-9; N = 102). RR of death comparing patients with recent systemic anticancer therapy to no treatment was 1.17 (95% CI, 0.83-1.64; N = 736). Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, have a high risk of dying. Patients ≥60 years have significantly higher mortality; pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death.
The combinations of antibody–drug conjugates (ADCs) with cytotoxic chemotherapy are challenged by overlapping toxicities, which may be lessened with newer generation and more tumor-selective ...ADCs.Complex interplay between ADCs and molecularly targeted agents may overcome treatment resistance of both drug classes and mitigate clonal heterogeneity.Multiple mechanisms support the combination of ADCs with immune checkpoint inhibitors such as induction of immunogenic cell death and increase of T cell infiltration in the tumor microenvironment.Clinical trial designs should consider the potential for pharmacological interactions and evaluate target response relationship in the combinatorial setting.
Antibody–drug conjugates (ADCs) have become a credentialled class of anticancer drugs for both solid and hematological malignancies, with regulatory approvals mainly as single agents. Despite extensive preclinical and clinical efforts to develop rational ADC-based combinations, to date only a limited number have demonstrated survival improvements over standard of care. The most appealing partners for ADCs are those that offer additive or synergistic effects on tumor cells or their microenvironment without unacceptable overlapping toxicities. Coadministration with antiangiogenic compounds, HER2-targeting drugs, DNA-damage response agents and immune checkpoint inhibitors (ICIs) represent active forerunners. Through the identification of targets with tumor-specific expression, improved conjugation technologies, and novel linkers and payloads offering superior therapeutic indices, the next generation of ADCs brings optimism to combinatorial approaches.
Background
Botulinum toxin type A (BoNTA) is a neurotoxin that acts by inhibiting the release of neurotransmitters acetylcholine at neuromuscular junctions, thus reducing muscular contractions. ...Recent evidence suggests that BoNTA can reduce nociceptive activities of sensory neurons in animal models by inhibiting release of certain neuropeptides. Despite the therapeutic benefit of BoNTA in alleviating painful muscle spasms, its efficacy in other musculoskeletal pain conditions is less clear.
Objective
We aim to examine the efficacy of BoNTA in reducing chronic musculoskeletal pain.
Methods
Studies for inclusion in our report were identified using MEDLINE, EMBASE, PUBMED, Cochrane Central Register of Controlled Trials, CINAHL, and reference lists of relevant articles. Studies were considered eligible for inclusion if they were randomized controlled trials (RCTs), evaluating the efficacy of BoNTA injections in pain reduction. All studies were assessed and data were abstracted independently by paired reviewers. The outcome measures were baseline and final pain scores as assessed by the patients. The internal validity of trials was assessed with the Jadad scale. Disagreements were resolved through discussions.
Main results
Twenty-one studies were included in the systematic review and 15 of them were included in the final meta-analysis. There was a total of 706 patients in the meta-analysis, represented from trials of plantar fasciitis (
n
= 1), tennis elbow (
n
= 2), shoulder pain (
n
= 1), whiplash (
n
= 3), and myofascial pain (
n
= 8). Overall, there was a small to moderate pain reduction among BoNTA patients when compared to control (SMD = −0.27, 95% CI: −0.44 to −0.11). When the results were analyzed in subgroups, only tennis elbow (SMD = −0.44, 95% CI: −0.86 to −0.01) and plantar fasciitis (SMD = −1.04, 95% CI: −1.68 to −0.40) demonstrated significant pain relief. Although not in the meta-analysis, one back pain study also demonstrated positive results for BoNTA. Lastly, BoNTA was effective when used at ≥25 units per anatomical site or after a period ≥5 weeks.
Conclusion
In our meta-analysis, BoNTA had a small to moderate analgesic effect in chronic musculoskeletal pain conditions. It was particularly effective in plantar fasciitis, tennis elbow, and back pain, but not in whiplash or shoulder pain patients. However, more evidence is required before definitive conclusions can be drawn. On the other hand, there is convincing evidence that BoNTA lacks strong analgesic effects in patients with myofascial pain syndrome. A general dose-dependent and temporal response with BoNTA injections was also observed.
Painful vaso-occlusive crisis (VOC) is the most common reason for hospitalization in children with sickle cell disease.
To benchmark pain outcomes in sickle cell disease, including process outcomes ...(eg, pain assessment and documentation practices, pain management interventions) and clinical outcomes (eg, pain intensity over hospital stay), to identify areas for improvement.
A retrospective study was conducted on electronic charts of children hospitalized with a primary diagnosis of VOC between July 2007 and August 2008.
A convenience sample of 50 admissions was used. In terms of clinical outcomes, patients presented to the emergency department with an initial median pain intensity of 9⁄10 (interquartile range 8⁄10 to 10⁄10). Forty-three per cent had not used opioids for pain relief at home. The mean (± SD) length of stay was 4.0±2.3 days. For most patients, median scores for highest daily pain intensity remained moderate to high throughout hospitalization, although scores did decrease significantly per day of hospitalization. In terms of process outcomes, pain intensity was assessed according to hospital standards on 25% of days in both the emergency department and the ward. There was no discrepancy between prescribed and administered opioid doses and medication use. In 95% of cases, strong opioid use was in a subtherapeutic or low therapeutic dosage range.
The results showed three areas to target for improvement: improved pain assessment and documentation using valid pain tools; more aggressive multimodal management for peak VOC pain; and better education and support for pain management at home. Further studies are required to evaluate optimal pain treatment practices.
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