Current Hematologic Malignancy Reports最新文献

Purpose of review: Cutaneous T cell lymphomas (CTCLs) are comprised of a heterogenous group of non-Hodgkin lymphomas that can be difficult to treat and are often refractory to standard therapies. Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common subtypes, accounting for the majority of CTCLs. There is no standard of care, and no treatments are curative. In this review, we summarize the promising, recently reported data describing novel systemic agents for the management of MF/SS.

Recent findings: Clinical trials are currently exploring a number of agents, including novel chemotherapies, antibodies and antibody drug conjugates (ADCs), immunotherapy, and cellular therapies. These promising novel agents may expand the treatment landscape for MF/SS.

Purpose of review: More than a decade following the discovery of Calreticulin (CALR) mutations as drivers of myeloproliferative neoplasms (MPN), advances in the understanding of CALR-mutant MPN continue to emerge. Here, we summarize recent advances in mehanistic understanding and in targeted therapies for CALR-mutant MPN.

Recent findings: Structural insights revealed that the mutant CALR-MPL complex is a tetramer and the mutant CALR C-terminus is exposed on the cell surface. Targeting mutant CALR utilizing antibodies is the leading therapeutic approach, while mutant CALR-directed vaccines are also in early clinical trials. Additionally, chimeric antigen receptor (CAR) T-cells directed against mutant CALR are under evaluation in preclinical models. Approaches addressing the cellular effects of mutant CALR beyond MPL-JAK-STAT activation, such as targeting the unfolded protein response, proteasome, and N-glycosylation pathways, have been tested in preclinical models. In CALR-mutant MPN, the path from discovery to mechanistic understanding to direct therapeutic targeting has advanced rapidly. The longer-term goal remains clonally-selective therapies that modify the disease course in patients.

Purpose of review: Multiple myeloma is a chronic malignancy and with evolving treatment options, understanding the economic burden and cost-effectiveness of therapies is crucial for clinicians and researchers.

Recent findings: In this, we review the recent approval of Bispecific antibodies and CAR-T for myeloma and their cost implications, including direct and indirect costs. We compare this to current regimens and provide cost comparisons in this review. We conclude that the use of more effective therapies such as CAR-T in earlier lines of therapies may be more cost-effective depending on the country and model used. Further studies are essential to better understand the cost-effectiveness of bispecific antibodies including head-to-head comparisons to CAR-T therapy.

Purpose of review: Peripheral neuropathy (PN) is more commonly seen in individuals with monoclonal gammopathies, especially in patients with an IgM monoclonal gammopathy or Waldenström macroglobulinemia.

Recent findings: There are multiple potential ways that the paraprotein may result in peripheral neuropathy. The diagnosis and management of monoclonal gammopathy-associated PN are challenging and necessitate a concerted effort between the hematologist/oncologist and the neurologist. This review describes the most common PN syndromes associated with monoclonal gammopathy, such as anti-myelin-associated glycoprotein neuropathy, light chain amyloidosis, cryoglobulinemia, POEMS, CANOMAD, and others. We also review the therapies used to treat these conditions.

Purpose of review: Recent studies show that unresolved disparities hinder enrollment to clinical trials, equitable distribution of treatments, and impact the generalizability of trials, compromising health outcomes across different populations. This review aims to examine the persistent disparities noted in clinical trial enrollment, with particular focus on lymphoid malignancies, CAR-T cell and bispecific antibody therapies.

Recent findings: Targeted interventions can enhance recruitment of underrepresented groups in clinical trials and address the complex barriers hindering participation, which are essential for achieving healthcare access equity and treatment outcomes. Improvement must be multifaceted, addressing socioeconomic, geographic, and biologic factors contributing to underrepresentation. This includes more lenient eligibility criteria, improving outreach and education, as well as using technology to diversify trial participation.

Purpose of the review: This study aimed to summarize evidence and provide consensus-based guidelines for management of transplantation in patients with telomere biology disorders (TBD). Specifically, this review focuses on clinical management of lung, liver, and bone marrow transplantation in TBD patients.

Recent findings: TBD patients have specific unique biological vulnerabilities such as T cell immunodeficiency, susceptibility to infections, hypersensitivity to chemotherapy and radiation, and cytopenias. Furthermore, multiple organ involvement at diagnosis makes clinical management especially challenging due to higher degree of organ damage, and stress-induced telomeric crisis. Sequential and combined organ transplants, development of novel radiation and alkylator-free conditioning regimen, and use of novel drugs for graft-versus-host disease prophylaxis are some of the recent updates in the field. Multidisciplinary management is essential to optimize transplant outcomes in patients with TBD. In this review, we provide consensus-based transplant management guidelines for clinical management of transplant in TBD.

Purpose of review: Graft-versus-host disease (GVHD) is a serious complication after allogeneic HCT. Recently, several pivotal studies have been conducted demonstrating significant improvements in the management of GVHD. Here, we review important trials pertaining to GVHD prevention, acute GVHD treatment, and treatment of steroid refractory acute and chronic GVHD.

Recent findings: Clinical trials in preventing GVHD demonstrate lower rates of severe acute GVHD and chronic GVHD with post-transplant cyclophosphamide. For acute GVHD, lower risk acute GVHD appears amenable to steroid-sparing therapies, such as sirolimus and itacitinib. Combinations with novel agents such as itolizumab appear promising for high risk acute GVHD. For steroid-refractory acute GVHD, ruxolitinib should be considered first line therapy. For chronic GVHD requiring therapy beyond steroids, ruxolitinib, belumosudil, and ibrutinib are now available and should be considered. Increasingly, GVHD has become a manageable complication after allogeneic HCT potentially translating to greater success with allogeneic HCT in the future.

Purpose of review: The introduction of bispecific antibodies is one of the most significant recent advances in the treatment of relapsed/refractory multiple myeloma. This review will summarize the management of the toxicities associated with newly approved T cell-engaging bispecific antibodies and those which may be approved in the near future.

Recent findings: Numerous trials have shown that bispecific antibodies can be both effective and tolerable when adverse events are properly managed. Cytokine release syndrome and increased infections are observed across all bispecific antibodies. Additional adverse events are target-specific, such as the more severe hypogammaglobulinemia and infections of BCMA bispecific antibodies and the dysgeusia, nail dystrophy, and skin changes of GPRC5D bispecific antibodies. Bispecific antibodies will surely become a mainstay of multiple myeloma therapy given their efficacy and accessibility. Their unique toxicities must be carefully considered and managed to ensure they are utilized safely.

Purpose of review: Allogeneic hematopoietic cell transplantation is the only potentially curative treatment for myelofibrosis. This review discusses issues not well-covered by existing guidelines: timing of transplant, pre-transplant spleen management and alternative donors; providing our approach to these situations.

Recent findings: Research continues to allow better identification, by better risk stratification and advances in understanding likelihood of durable JAKi response, which patients are likely to derive benefit from upfront transplant versus those for whom delayed transplant may be more appropriate. Several options of JAKi therapy provide a non-surgical option for pre-HCT splenomegaly management, allowing some patients to avoid risks associated with splenectomy. Recent years have also seen a sharp spike in haploidentical donor transplants, along with narrowing of the gap in outcomes between donor types. Continuous enrollment in prospective studies or well-designed registries is required to generate the high-quality data needed to develop better decision tools for these scenarios.

Purpose of review: Given the poor outcomes for peripheral T-cell lymphomas (PTCL), stem cell transplant (SCT) remains an important therapeutic approach. Post-SCT relapse is common and maintenance therapy post-SCT is increasingly being utilized. Here we review the use of post-SCT maintenance therapy for PTCL patients.

Recent findings: Maintenance therapy is increasingly utilized to decrease post-SCT relapse and improve outcomes in PTCL. Ongoing and completed post-SCT maintenance trials utilizing agents such as romidepsin, brentuximab vedotin, duvelisib, and pembrolizumab have shown efficacy in decreasing relapse. Further, additional agents with efficacy in PTCL have emerged that may inform future maintenance approaches. Maintenance therapy is a promising approach to maintain response after SCT in PTCL. While several trials are ongoing to evaluate maintenance therapy in PTCL, current data suggests this may be an effective method to decrease post-SCT relapse.