Durable responses in acute lymphoblastic leukaemia with the use of FLT3 and IDH inhibitors.

Data regarding the use of FMS-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase 1/2 (IDH1/2) inhibitors in acute lymphoblastic leukaemia (ALL) are lacking. We identified 14 patients with FLT3- or IDH1/2-mutated ALL. Three early T-cell precursor-ALL patients received FLT3 or IDH2 inhibitors. Patient 1 maintains a complete remission (CR) with enasidenib after intolerance to chemotherapy. Patient 2 maintained a CR for 27 months after treatment with enasidenib for relapsed disease. Patient 3 was treated with venetoclax and gilteritinib at the time of relapse and maintained a CR with gilteritinib for 8 months. These cases suggest that FLT3 and IDH inhibitors could represent a viable therapeutic option for ALL patients with these mutations.

Expedited evaluation of hereditary hematopoietic malignancies in the setting of stem cell transplantation.

Not available.

Primary ovarian insufficiency secondary to chemotherapy with inotuzumab ozogamicin and other agents.

Recent advances in targeted therapy with monoclonal antibodies have significantly improved outcomes for people with cancer, sometimes allowing patients to avoid ovotoxic agents altogether. The current understanding is that monoclonal antibody cancer therapies that are not targeted to ovarian antigens should not impact ovarian reserve or increase the risk of primary ovarian insufficiency (POI). We present a case of rapid onset POI in a 23-year-old patient following chemotherapy for relapse/refractory B-cell acute lymphoblastic leukemia with a monoclonal antibody drug-conjugate, inotuzumab ozogamicin, that targets CD22. She was also treated with intrathecal methotrexate, cytarabine, and vincristine which are typically considered low risk for ovotoxicity. She was ovulatory with an AMH of 1.0 ng/mL prior to treatment and 2 months later was found to have an undetectable AMH. The patient experienced a canceled fertility preservation cycle due to an absent response to gonadotropins during ovarian stimulation. Consideration should be given to potential gonadal effects of monoclonal antibody therapies that may not have previously been explored.

Gaps in Adolescent and Young Adult Cancer Education in Oncology Fellowship Training.

Purpose: Adolescents and young adults (AYAs, 15-39 years) with cancer experience disparities in care and outcomes compared with older/younger patients. AYAs receive care from medical and pediatric oncologists, however, little is known about the extent of training fellows receive. This needs assessment evaluating current AYA oncology (AYA-O) education in pediatric and medical oncology fellowship programs to identify knowledge gaps for curricular development. Methods: An anonymous, cross-sectional, web-based survey developed by pediatric and medical oncologists was sent to medical (n = 178) and pediatric (n = 119) hematology/oncology program directors (PDs) at 251 sites in the United States. PDs were asked to participate and distribute the survey to their fellows. Survey questions addressed current AYA curriculum, provider comfort, and priorities for future AYA educational content. Results: Participants from 69/251 programs responded (program response rate = 27%), including 51 PDs (32 pediatric, 19 medical oncology) and 58 fellows (33 pediatric, 25 medical oncology). Eighty-five percent of PDs (44/51) reported lacking formal AYA curricula. Of these, 80% (35/44) offer some topic-specific lectures, while 20% (9/44) provide little/no education for any topics. For nearly all topics, at least 45% of combined respondents reported little/no education. Respondents believe AYA topics are important for inclusion in future curricula. The most important topics for inclusion reported were oncofertility (82%), survivorship (78%), and communication (77%). Conclusions: There are large and actionable gaps in AYA-O education during fellowship training. Efforts are underway to develop AYA-O curriculum to provide both medical and pediatric oncology fellows with the knowledge and skills required to provide optimal AYA care.

Health Care Resource Utilization and Total Costs of Care for Adult Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia in the United States: A Retrospective Claims Analysis.

PURPOSE: Although immunotherapies such as blinatumomab and inotuzumab have led to improved outcomes, financial burden and health resource utilization (HRU) have increased for adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). This study assessed real-world HRU and costs of care among adult patients with R/R B-ALL by line of therapy (LoT) in the United States. METHODS: We selected patients from the MarketScanⓇ Database (January 1, 2016 through December 31, 2020) as follows: ≥1 claims of ALL-indicated first-line (1L) therapies, ≥1 diagnosis of ALL before the index date (1L initiation date), 6-month continuous enrollment before the index date, second-line (2L) therapy initiation, ≥18 years old at 2L, no clinical trial enrollment, no diagnosis of other forms of non-Hodgkin's lymphoma, and no claim for daratumumab or nelarabine during the study period. Outcome measures included claim-based time to next treatment (TTNT), all-cause and adverse event (AE)-related HRU, and all-cause and AE-related costs. FINDINGS: The R/R B-ALL cohort (N = 203) was 60% male, median age of 41 years, and median Charlson Comorbidity Index score of 3.0. Mean (SD) follow-up was 17.8 (11.8) months. Of those who received 2L, 55.7% (113/203) required 3L, and 15% (30/203) initiated 4L+. Patients relapsed quickly, with a median TTNT of 170 days, 169 days, and 205 days for 2L, 3L, and 4L+, respectively. Hospitalization rates were high across each LoT (2L, 88%; 3L, 73%; 4L+, 73%), and the mean (SD) inpatient length of stay increased by LoT as follows: 8.6 (6.8) days for 2L, 10.6 (13.3) for 3L, and 11.6 (13.6) for 4L+. Mean (SD) overall costs were substantial within each LoT at $513,279 ($599,209), $340,419 ($333,555), and $390,327 ($332,068) for 2L, 3L, and 4L+, respectively. The mean (SD) overall/per-patient-per-month AE-related costs were $358,676 ($497,998) for 2L, $202,621 ($272,788) for 3L, and $210,539 ($267,814) for 4L+. Among those receiving blinatumomab or inotuzumab within each LoT, the mean (SD) total costs were $566,373 ($621,179), $498,070 ($376,260), and $512,908 ($159,525) for 2L, 3L, and 4L+, respectively. IMPLICATIONS: These findings suggest that adult patients with R/R B-ALL relapse frequently with standard of care and incur a substantial HRU and cost burden with each LoT. Those treated with blinatumomab or inotuzumab incurred higher total costs within each LoT compared with the overall R/R B-ALL cohort. Alternative therapies with longer duration of remission are urgently needed, and HRU should be considered for future studies examining the optimal sequencing of therapy.

Developing Targeted Therapies for T Cell Acute Lymphoblastic Leukemia/Lymphoma.

PURPOSE OF REVIEW: Largely, treatment advances in relapsed and/or refractory acute lymphoblastic leukemia (ALL) have been made in B cell disease leaving T cell ALL reliant upon high-intensity chemotherapy. Recent advances in the understanding of the biology of T-ALL and the improvement in immunotherapies have led to new therapeutic pathways to target and exploit. Here, we review the more promising pathways that are able to be targeted and other therapeutic possibilities for T-ALL. RECENT FINDINGS: Preclinical models and early-phase clinical trials have shown promising results in some case in the treatment of T-ALL. Targeting many different pathways could lead to the next advancement in the treatment of relapsed and/or refractory disease. Recent advances in cellular therapies have also shown promise in this space. When reviewing the literature as a whole, targeting important pathways and antigens likely will lead to the next advancement in T-ALL survival since intensifying chemotherapy.

Health resource utilization and costs of care for adult patients with relapsed or refractory mantle cell lymphoma in the United States: a retrospective claims analysis.

OBJECTIVES: We assessed real-world healthcare resource utilization (HRU) and costs among US patients with relapsed or refractory mantle cell lymphoma (R/R MCL) by line of therapy (LoT). METHODS: We selected patients from MarketScan® (1/1/2016-12/31/2020): ≥1 claims of MCL-indicated first line (1L) therapies, ≥1 diagnoses of MCL pre-index date (1L initiation date), ≥6-month continuous enrollment pre-index date, second line (2L) therapy initiation, ≥18 years old at 2L, and no clinical trial enrollment. Outcomes included time to next treatment (TTNT), all-cause HRU, and costs. RESULTS: The cohort (N = 142) was 77.5% male, aged 62 years (median). Sixty-six percent and 23% advanced to 3L and 4L+, respectively. Mean (median) TTNT was 9.7 (5.9), 9.3 (5.0), and 6.3 (4.2) months for 2L, 3L, and 4L+, respectively. Mean (median) per patient per month (PPPM) costs were $29,999 ($21,313), $29,352 ($20,033), and $30,633 ($23,662) for 2L, 3L, and 4L+, respectively. Among those who received Bruton tyrosine kinase inhibitors, mean (median) PPPM costs were $24,702 ($17,203), $31,801 ($20,363), and $36,710 ($25,899) for 2L, 3L, and 4L+, respectively. CONCLUSIONS: During the period ending in 2020, patients relapsed frequently, incurring high HRU and costs across LoTs. More effective treatments with long-lasting remissions in R/R MCL may reduce healthcare burden.

Mantle cell lymphoma is a rare blood cancer of white blood cells. This type of cancer can be hard to treat, even with new treatments. In about 15% to 20% of people, the cancer will not get better or will come back within 2 years of starting treatment. When this happens, there are few good options for treatments that work. Using medical claims data, we looked at healthcare use and costs among US patients with mantle cell lymphoma that came back after treatment or did not respond to treatment. We found 142 patients who met the study criteria. Of these, 77.5% were men with a median age of 62 years. Sixty-six percent got a third of the treatment and 23% got a fourth treatment or more. The time until the next treatment was about 9­10 months for patients who got a second and third treatments.. It was about 6 months for people who got a fourth or more treatment. The average monthly cost of treatment was about $30,000 for those receiving a second or fourth or more treatment. It was slightly less for those who got a third treatment. For those who got Bruton's tyrosine kinase inhibitors, the monthly costs went up with each treatment they needed. Overall, we found that during the study period, patients with mantle cell lymphoma worsened quickly, received multiple treatments, and had high costs of care. Better treatments that work longer are needed.

Effectiveness of cognitive behavioral therapy in improving functional health in cancer survivors: A systematic review and meta-analysis.

BACKGROUND: Cancer survivors suffer from health deficits caused by their disease and treatment. This study conducted a systematic review and meta-analysis on how, and to what extent, cognitive-behavioral therapy (CBT) impacts functional health outcomes in cancer survivors. METHODS: We searched 7 electronic databases, 91 published review articles, and 4 professional websites for eligible randomized and non-randomized controlled trials focusing on cancer survivors. RESULTS: We included 95 studies published between 1986 and 2021. Risk of bias across studies was low overall. We identified an overall statistically significant treatment effect size across functional health categories, d = 0.391, p < 0.001, and significant moderators associated with CBT's treatment effect, i.e., treatment phase and type of comparison. CONCLUSIONS: CBT was effective at improving functional health outcomes of cancer survivors, regardless of therapy delivery modality or number of cancer diagnoses patients had, but not for newly diagnosed patients or those currently benefiting from an active comparator intervention.

Evaluating the Feasibility and Acceptability of an Artificial-Intelligence-Enabled and Speech-Based Distress Screening Mobile App for Adolescents and Young Adults Diagnosed with Cancer: A Study Protocol.

Adolescents and young adults (AYAs) diagnosed with cancer are an age-defined population, with studies reporting up to 45% of the population experiencing psychological distress. Although it is essential to screen and monitor for psychological distress throughout AYAs' cancer journeys, many cancer centers fail to effectively implement distress screening protocols largely due to busy clinical workflow and survey fatigue. Recent advances in mobile technology and speech science have enabled flexible and engaging methods to monitor psychological distress. However, patient-centered research focusing on these methods' feasibility and acceptability remains lacking. Therefore, in this project, we aim to evaluate the feasibility and acceptability of an artificial intelligence (AI)-enabled and speech-based mobile application to monitor psychological distress among AYAs diagnosed with cancer. We use a single-arm prospective cohort design with a stratified sampling strategy. We aim to recruit 60 AYAs diagnosed with cancer and to monitor their psychological distress using an AI-enabled speech-based distress monitoring tool over a 6 month period. The primary feasibility endpoint of this study is defined by the number of participants completing four out of six monthly distress assessments, and the acceptability endpoint is defined both quantitatively using the acceptability of intervention measure and qualitatively using semi-structured interviews.

Updates in the Management of Relapsed and Refractory Acute Lymphoblastic Leukemia: An Urgent Plea for New Treatments Is Being Answered!

The treatment of acute lymphoblastic leukemia (ALL) has dramatically changed over the past three decades. However, relapsed and/or refractory ALL still remains with a very low survival and high morbidity associated with its treatment. Here, we will review the outstanding progress that has been made in the treatment of relapsed and/or refractory ALL and discuss future directions and challenges that require further investigation.

Examining the Pathoplastic Moderating Role of Education on the Association between Depressive Mood and Self-Rated Health among Cancer Survivors: A Population-Based Study.

OBJECTIVE: Self-rated health (SRH) is a salient patient outcome for cancer survivors, and depressive mood and education are known determinants of cancer survivors' SRH. Moving beyond the well-established direct association between depressive mood, education, and SRH among cancer survivors, this epidemiological study investigated the pathoplastic role of education on depressive mood in relation to SRH among a nationally representative sample of cancer survivors in the United States. METHODS: The 2019 National Health Interview Survey was analyzed using data from adult participants (≥18 years old) who self-reported as cancer survivors (n = 3844). Ordered logistic regression was used to evaluate the direct impact of depressive mood and education in relation to SRH. In addition, the pathoplastic moderating effect was evaluated using ordered logistic regression with an interaction term of depressive mood and education in the regression model. All analyses adjusted for complex sample weights so that findings are nationally representative. RESULTS: After adjusting for all covariates, U.S. cancer survivors' depressive mood was significantly associated with lower SRH, and U.S. cancer survivors' higher education was significantly associated with higher SRH. As a pathoplastic moderator, cancer survivors' education significantly moderated the association between depressive mood and SRH. The negative association between depressive mood and SRH was significantly greater among those with higher education. CONCLUSION: Moving beyond the direct association between depressive mood, education, and SRH, education served as a pathoplastic moderator in relation to depressive mood and SRH. Psycho-oncology providers need to be mindful of the "protective-risk" effect of education in relation to cancer survivors' depressive mood and SRH.

Efficacy and tolerability of a modified pediatric-inspired intensive regimen for acute lymphoblastic leukemia in older adults.

Although acute lymphoblastic leukemia (ALL) is most common in pediatric and adolescent and young adult (AYA) patients, 20% of cases are diagnosed in patients ≥ 55 years old. Use of intensive pediatric regimens in AYA populations has demonstrated excellent tolerability and significant improvements in event-free survival (EFS) and overall survival (OS). The backbone of pediatric regimens includes asparaginase and corticosteroids, both of which are associated with more toxicity in older patients and those with body mass index (BMI) ≥ 30 kg/m which leads to poor tolerance of these regimens. We tested the safety and efficacy of a dose-modified The Cancer and Leukemia Group B 10403 regimen using reduced doses of pegylated (PEG)-asparaginase (ASP) and corticosteroids (RD-10403) in 30 patients with Philadelphia-chromosome negative ALL who were ≥50-year-old and younger adults with significant metabolic or hepatic co-morbidities. The complete remission rate on day 28 was 77%, 3-year EFS was 54%, and estimated 3-year OS was 55%. Grade 3+ toxicity was noted in 40% of patients during induction, and induction-related mortality was 3%. Additional prospective evaluation of RD-10403 is merited to determine efficacy and safety of this regimen and to serve as a framework for chemoimmunotherapy combination therapy.

Age-Stratified Profiles of Serum IL-6, IL-10, and TNF-α Cytokines Among Kenyan Children with Schistosoma haematobium, Plasmodium falciparum, and Other Chronic Parasitic Co-Infections.

In a study of children having polyparasitic infections in a Schistosoma haematobium-endemic area, we examined the hypothesis that S. haematobium-positive children, compared with S. haematobium-negative children (anti-soluble worm antigen preparation [SWAP] negative and egg negative) have increased systemic production of pro-inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α) and decreased down-regulatory IL-10. A total of 804 children, 2-19 years of age, were surveyed between July and December 2009 and tested for S. haematobium, Plasmodium falciparum, filariasis, and soil-transmitted helminth infections. Plasma levels of IL-6, TNF-α, and IL-10 were compared for S. haematobium-positive and S. haematobium-negative children, adjusting for malaria, filaria, and hookworm co-infections, and for nutritional status, age group, sex, and geographic location. IL-10 was significantly elevated among children infected with S. haematobium, showing bimodal peaks in 7-8 and 13-14 years age groups. IL-10 was also higher among children who were acutely malnourished, whereas IL-10 levels were lower in the presence of S. haematobium-filaria co-infection. After adjustment for co-factors, IL-6 was significantly elevated among children of 5-6 years and among those with P. falciparum infection. Lower levels of IL-6 were found in malaria-hookworm co-infection. High levels of TNF-α were found in children aged 11-12 years regardless of infection status. In addition, village of residence was a strong predictor of IL-6 and IL-10 plasma levels. In adolescent children infected with S. haematobium, there is an associated elevation in circulating IL-10 that may reduce the risk of later morbidity. Although we did not find a direct link between S. haematobium infection and circulating pro-inflammatory IL-6 and TNF-α levels, future T-cell stimulation studies may provide more conclusive linkages between infection and cytokine responses in settings that are endemic for multiple parasites and multiple co-infections.

Development of a specimen-sparing multichannel bead assay to detect antiparasite IgG4 for the diagnosis of Schistosoma and Wuchereria infections on the coast of Kenya.

To better delineate the impact of parasitic coinfection in coastal Kenya, we developed a novel specimen-sparing bead assay using multiplex flow immunoassay (MFI) technology to simultaneously measure serum or plasma immunoglobulin G4 (IgG4) against Brugia malayi antigen (BMA) and Schistosoma haematobium soluble worm antigen (SWAP). Properties of the bead assay were estimated by latent class analysis using data from S. haematobium egg counts/filarial rapid diagnostic cards (RDTs), parasite-specific enzyme-linked immunosorbent assays (ELISAs), and the multichannel IgG4 assay. For schistosomiasis, the bead assay had an estimated sensitivity of 81% and a specificity of 45%, and it was more sensitive than ELISA or urine egg counts for diagnosing infection. For filariasis, it had a sensitivity of 86% and a specificity of 39%, and it was more sensitive than ELISA or RDT. Measuring antibody by MFI is feasible and may provide more accurate epidemiological information than current parasitological tests, especially in the setting of low-intensity infections.