ALL Hub

During the ALL Hub Steering Committee meeting, Wendy Stock chaired a discussion on optimizing treatment for adults with relapsed/refractory Philadelphia chromosome-negative B-cell ALL.

During the ALL Hub Steering Committee meeting, André Baruchel chaired a discussion on “What are the key considerations when preparing patients with ALL for CAR T-cell therapy ?”, featuring Andrea Biondi, Anita Rijneveld, and José María Ribera. The discussion topics included: Key considerations when selecting patients: stable disease, degree of antigen expression, burden of bone marrow disease, and number of circulating tumor blasts Bridging therapy and lymphodepletion considerations The impact of prior exposure to blinatumomab and inotuzumab on CAR T-cell outcomes Indications for the use of tisagenlecleucel in pediatric ALL  Indications for the use of brexucabtagene autoleucel in adult ALL

This series of podcasts covers global socioeconomic disparity in ALL. In this episode, the ALL Hub asked Eduardo Chapchap, Hospital Israelita Albert Einstein, São Paulo, BR and Federico Antillion, Unidad Nacional de Oncologia Pediatrica, Guatemala City, GT about disparities in toxicity and their management in ALL, including:·       What are the toxicities you encountered while treating patients with ALL and how did you manage them? ·       What are the barriers contributing to poor toxicity management? Chapchap and Antillion discussed socioeconomic disparities in ALL across high middle-income countries (HMIC), low middle-income countries (LMIC), and within adult and pediatric populations. Chapchap mentioned common toxicities such as infections and neutropenia, which are becoming easier to manage considering the increased access to antifungal medications, antibiotics, and preventative measures. Early and long-term neurological toxicities are also common and, although these are more challenging to manage, there are preventative measures in place, such as reducing the dose of cytarabine and methotrexate, reducing the dose in older patients, omitting the use of cranial radiation, and supportive care measures. Other adverse effects, include asparaginase-related toxicities such as thrombosis in adult patients, are generally treated with prophylactic heparins and/or avoiding fibrinogen replacement. Hypertriglyceridemia and liver toxicities are common asparaginase toxicities that are often managed by dose reductions in patients who are overweight. Antillion discussed that febrile neutropenia and septic shock are often related to chemotherapy induction. Infection management involves the use of different types of prophylactic measures. Bleeding events also occur, which are related to a low platelet count. While patients can face asparaginase-related toxicities, the most common toxicities are severe cases of acute pancreatitis. Anthracycline-based medication can cause medium and long-term cardiac toxicities in pediatric ALL, which can impact quality of life. 

This series of podcasts covers global socioeconomic disparity in ALL. In this episode, the ALL Hub asked Eduardo Chapchap, Hospital Israelita Albert Einstein, São Paulo, BR and Federico Antillion, Unidad Nacional de Oncologia Pediatrica, Guatemala City, GT about the treatment challenges in ALL, including:•         Do treatment outcomes differ among race and ethnicity? Why do you think this is? •         What are the obstacles to treatment adherence?•         How do you sequence treatment in relapsed/refractory (R/R) B-ALL?Chapchap and Antillion discussed socioeconomic disparities in ALL across high middle-income countries (HMIC), low middle-income countries (LMIC), and within adult and pediatric populations. Chapchap highlighted that treatment adherence is more of a challenge in childhood versus adult ALL. Factors impacting adherence include concern among patients about the short and long-term adverse effects of treatment. Additionally, some patients misunderstand the importance of treatment adherence, and thus communication should be increased between patients and their physicians. Psychological issues amongst adolescent patients in particular can affect adherence to treatment. Social and economic barriers, such as distance from the centers and familial issues, can also cause low adherence to treatment. Antillion mentioned the educational level of the family and language barriers as the main obstacles to treatment adherence. Treatment adherence remains particularly challenging in the adolescent population. Across the public systems in Brazil, there is currently no access to immunotherapies for R/R B-cell ALL, though blinatumomab could be approved for early marrow relapses for children in the near future. In the private settings, there is access to blinatumomab, inotuzumab ogamacin (InO), and CD19-directed chimeric antigen receptors (CAR) T-cell therapies. Important factors in deciding the sequencing of immunotherapies include tumor burden, timing of relapse, CD19/CD20 expression, and prior regimens. For patients who are minimal residual disease-positive with bone marrow relapses, blinatumomab could be an ideal option. For those with high tumor burden with early and/or primary refractory disease, InO would be a suitable option followed by blinatumomab or stem cell transplantation consolidation. For late relapse, cytoreductive therapy with pediatric-inspired regimens followed by blinatumomab consolidation could be an option. CAR T-cell therapies are generally reserved for post stem cell transplantation. In Guatemala, sequencing of treatment depends on the timing of relapse, tumor burden, and whether there are new or different translocations. For standard or intermediate-risk patients with late relapse conventional chemotherapy is given. High-risk patients with early relapse are directed to other treatment options outside of Guatemala, as there is currently no access to blinatumomab, InO or CAR T-cell therapy, and in some cases patients will receive palliative and supportive care.

This series of podcasts covers global socioeconomic disparity in ALL. In this episode, the ALL Hub asked Eduardo Chapchap, Hospital Israelita Albert Einstein, São Paulo, BR and Federico Antillion, Unidad Nacional de Oncologia Pediatrica, Guatemala City, GT about the diagnostic challenges in ALL, including:•         What are the barriers to understanding the genetics of ALL? •         Is there a lack of MRD, cytogenetic, and molecular testing in the real-world setting? •         Does this affect your approaches to managing patients?Chapchap and Antillion discussed socioeconomic disparities in ALL across high middle-income countries (HMIC), low middle-income countries (LMIC), and within adult and pediatric populations. Chapchap highlighted the lack of resources and genetic tests in Brazil, with some centers only having access to karyotyping and BCR::ABL testing. Also, the clonal heterogeneity of ALL presents challenges in diagnosis, and the literature is divided on the best molecular testing methods for assessing genetic alterations. Given that fewer cases of ALL are seen in adults, most of the genetic testing is restricted to research settings. The timing of results, which can sometimes take some months, also presents a challenge and possibly delays the timing of therapy. Antillion echoed that there is limited access to molecular diagnostics in Guatemala, with testing only currently available for BCR::ABL, ETV::RUNX1, 4:11 and 1:11 translocations. Similarly, there is also no access to cytogenetics, though access to MRD testing has been recently available in a limited capacity. Overall, the limited access to resources and state of the art techniques as well as delays in receiving results can affect the management of patients with ALL. 

Felice and Fleming discussed socioeconomic disparities in ALL across high middle-income countries (HMIC), low middle-income countries (LMIC), and within adult and pediatric populations. Felice shared that the extensive diagnostic landscape in Argentina, including 25 centers focused on performing flow cytometry and flow minimal residual disease (MRD) assessments, and another 15 centers with a focus on genetic analyses presents a challenge. She highlighted the lack of human resources and training, particularly in genetic analyses, the logistical challenges in the shipping of samples, the disparities in access to diagnostic tests across the centers, and the persuasion of others about the relevance of different diagnostic testing. Fleming echoed that convincing others about the value of specific diagnostic tests has been difficult across adult centers in Australia and has followed a sequential process over the years, first with genetic testing and more recently with the acceptance of MRD testing across all centers; although variation in diagnostic procedure exists. Overall, larger centers have widely accepted and adopted these diagnostic techniques though smaller and regional centers, with fewer cases of ALL, are gradually getting to a wider stage of acceptance. Public funding for diagnostic testing is often more difficult to acquire than funding for therapeutics and this impacts diagnosis overall.Felice and Fleming both commented on how access to diagnostic procedures affects the management of patients locally. Felice highlighted that convincing private hospitals on accreditation of MRD testing is a difficult process compared with public hospitals due to there being fewer cases of ALL, economic issues, and lack of quality of control which affects the survival rates of patients. Smaller centers with fewer cases and/or specific regions with less access to medications and lower management of complications and toxicities in both LMICs and HMICs also affects survival rates.