Progress and change also mean new challenges

The annual meeting of the American Society of Hematology is the world’s most important and comprehensive congress in hematologic oncology. International experts exchange information on current research results and the most important innovations in therapy and diagnosis in numerous sessions. Many different aspects come into play – from quality of life to new challenges.

A new study addressed the quality of life of patients after CAR-T cell therapy. Chimeric antigen receptor T-cell (CAR-T) therapy has transformed cancer treatment, but relatively few studies have examined the impact of therapy on patients’ quality of life over the long-term – an aspect of treatment that often suffers when treated with traditional intensive anticancer drugs such as chemotherapy. A new study found that the well-being of patients with blood cancer improved significantly six months after treatment with CAR T-cell therapy. To conduct this study, researchers enrolled 103 patients aged 23 to 90 years with a blood cancer diagnosis from April 2019 to November 2021. Lymphoma was diagnosed in 71% of these patients, myeloma in 28%, and B-cell acute lymphoblastic leukemia in 1%. Patients eligible for CAR-T therapy most commonly received tisagenlecleucel (34%), lisocabtagene maraleucel (16%), axicabtagene ciloleucel (13%), and idecabtaene vicleucel (12%).

CAR-T therapies are developed by taking a patient’s own T cells and modifying them to target specific proteins on the surface of cancer cells. These altered T cells are then reintroduced into the patient’s immune system to kill the cancer cells. In this way, the treatment of patients with relapsed and refractory blood cancers has been revolutionized. However, it remains a unique treatment with unique toxicities, including cytokine release syndrome, an inflammatory flu-like illness, and neurologic toxicities. And these complications can be very stressful for patients.

The researchers used self-report questionnaires to measure quality-of-life variables at specific time intervals, including before CAR T-cell infusion and one week, one month, three months, and six months after CAR T-cell infusion. Quality of life was measured with a 27-item questionnaire, the Functional Assessment of Cancer Therapy-General (FACT-G). Overall, 76% of patients achieved remission, and 33% experienced immune effector cell-associated neurotoxicity syndrome, a common side effect of CAR-T therapy. Of note, 38% of patients did not survive the follow-up period of the study. The researchers were particularly interested in understanding how CAR-T cell therapy affects patients’ quality of life. They found that quality of life in most patients initially declined (from a mean baseline of 77.9 to 70.1) during the first week after CAR T-cell therapy administration – a time when treatment-related symptoms tend to be most pronounced – and then increased significantly (to a mean of 83.7) by six months post-infusion. Improvements were also noted in physical symptom burden and anxiety symptoms. While most study participants ultimately experienced an improvement in their quality of life, approximately 20% of patients experienced persistent physical and psychological symptoms that temporarily impaired quality of life.

Life expectancy of patients with sickle cell disease

While research has long identified disparities in health outcomes among people with sickle cell disease (SCD), few studies have quantified these differences. A new study now finds that the average life expectancy of publicly insured patients with sickle cell anemia is about 52.6 years. In contrast, the average life expectancy in the United States is 73.5 years for men and 79.3 years for women, demonstrating the significant burden that SCD can place on affected populations. SCD is the most common inherited red blood cell disease in the United States, affecting an estimated 100,000 people.

The researchers analyzed data from Medicaid Analytic eXtract (MAX) files and Medicare Part A and B fee-for-service claims that included patients from 2008 to 2016. The data included demographic information, insurance enrollment status, and administrative claims for all individuals with SCD covered by Medicaid or Medicare in all 50 states. The study included 94616 individuals with SCD at an average age of 26.6 years and with different types of insurance. The authors reported that 5% of participants were insured through the Medicare Old-Age and Survivors Insurance Trust Fund (OASI), 4% through Medicare for disability or end-stage renal disease, 48% through Medicaid, and 43% through Medicare and Medicaid with dual eligibility. Of the study population, 74% were black. The researchers found that the average life expectancy for publicly insured individuals with SCD was 52.6 years, with men’s life expectancy at birth (49.3 years) significantly lower than women’s life expectancy at birth (55 years). However, the study also found that individuals covered by Medicare for disability or end-stage renal disease, as well as individuals covered by both Medicare and Medicaid, had significantly worse survival, with an average life expectancy at birth of 51.1 years. Differences in life expectancy for people with SCD across public insurance most likely reflect differences in the burden of comorbidities. In recent decades, several care-modifying medical interventions for SCD have been developed, such as newborn screening, pneumococcal vaccination, and prophylactic antibiotics, which have dramatically improved the life expectancy of children diagnosed with SCD.

It all depends on the size

According to the guidelines, surgical removal of lymph nodes is the standard for lymphoma diagnosis. However, core needle biopsy (CNB) has become accepted as part of lymphoma diagnostics in recent decades. The aim of a study was to present the largest multicenter inventory of lymph nodes harvested from patients with suspected lymphoma by either CNB or surgical excision and to compare their diagnostic performance in routine pathologic practice. A total of 32285 cases registered in the French lymphopathy network were reviewed. In addition, the percentage of cases correctly diagnosed with CNB and surgical excision according to the World Health Organization classification was evaluated. Although CNB provided a definitive diagnosis in 92.3% of cases and appeared to be a reliable method of investigation for most patients with suspected lymphoma, it was less informative than surgical excision, which provided a definitive diagnosis in 98.1% of cases. Discordance rates between referral and expert diagnoses were higher for CNB (23.1%) than for surgical excision (21.2%), and referring pathologists noted more cases with unclassified lymphoma or equivocal lesions by CNB. In such cases, expert review improved diagnostic workup by classifying ~90% of cases, with higher efficiency of surgical excision (93.3%) than CNB (81.4%). Furthermore, diagnostic agreement for reactive lesions was higher with surgical excision than with CNB. Although CNB allows accurate diagnosis of lymphoma in most cases, it increases the risk of incorrect or inconclusive conclusions. This large-scale survey also underscores the need for systematic expert review in cases of suspected lymphoma, particularly those involving CNB.

Challenges of progress

Advances and challenges in hematology, from pioneering bone marrow transplantation to developing targeted therapeutics, have transformed the treatment of blood disorders but also present new barriers, such as access to care, cost, and survival. More than 50 years ago, the first successful conditioned allogeneic bone marrow transplant (BMT) in humans gave hope to patients suffering from blood disorders. In the 1990s, virtually all BMT conditioning was myeloablative, donors were HLA-matched, the age limit of patients was about 40 years, and the cost was more than $400 000. Fewer than 20% of patients requiring BMT were eligible, and transplant-related mortality occurred in more than 20% of adults, with more than 50% of survivors suffering from acute and/or chronic graft-versus-host disease (GVHD). Today, BMT has become safer and more widely available thanks to better typing and supportive care.

At the same time, advances in genetics, molecular biology and immunology have led to targeted therapies that have the potential to cure many hematologic diseases or significantly extend life expectancy. In fact, these new drugs are so effective that indications for bone marrow transplantation (BMT) for hematologic malignancies are declining. For example, tyrosine kinase inhibitors are now synonymous with a cure for most patients with chronic myeloid leukemia. Monoclonal antibodies, bispecific T-cell engagers, Bruton tyrosine kinase inhibitors, CAR-T cells, and immune checkpoint inhibitors have reduced the need for BMT in pediatric and young adult ALL, relapsed aggressive B-cell lymphoma, Hodgkin’s lymphoma, and even multiple myeloma. Gene therapy and genome editing also have potential cures, but at a higher cost than BMT. Future indications for allogeneic BMT include severe autoimmune diseases (such as lupus and systemic sclerosis) and even solid organ transplantation (such as bone marrow/kidney) to prevent rejection and eliminate the need for long-term immunosuppressive therapy.

However, these tremendous advances also bring new challenges, such as funding these expensive therapies, training sufficient numbers of hematologists to meet the needs of a rapidly growing population, and shifting the focus to survivorship. It is also important to ensure that all patients have equal access to treatment and that clinical trials enroll patient populations that are representative of our diverse society.

Congress: ASH 2023