Pembrolizumab plus AVD for classical Hodgkin lymphoma, targeting the CD40/CD40-ligand axis in Waldenström Macroglobulinemia, and CXCR4-expressing CAR-cytokine induced killer cells in AML
In this week’s episode we’ll discuss the findings from a study exploring the combination of concurrent pembrolizumab, adriamycin, vinblastine, and dacarbazine in newly diagnosed classical Hodgkin lymphoma, learn more about the effects of targeting the CD40/CD40-ligand axis in Waldenström Macroglobulinemia, and review the findings from a study aimed at improving the bone marrow homing of CAR-cytokine induced killer cells in AML.
Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma
Lynch et al report on a single-arm study of concurrent pembrolizumab with doxorubicin, vinblastine, and dacarbazine (AVD) in 30 patients with untreated classic Hodgkin lymphoma (uCHL). Complete remission was documented in 90% of patients, and 2-year progression-free survival and overall survival were 97% and 100% respectively. Interestingly, circulating tumor DNA (ctDNA) appears to be a better predictor of outcome than positron emission tomography/computed tomography (PET-CT); of 4 patients with positive PET-CT and negative ctDNA at the end of therapy, none have relapsed. Though preliminary, concurrent PD-1 inhibition plus chemotherapy is a promising therapy for previously uCHL.
Selective homing of CAR-CIK cells to the bone marrow niche enhances control of the acute myeloid leukemia burden
Chimeric antigen receptor (CAR) T-cell therapy for acute myeloid leukemia has been disappointing, partially reflecting poor targeting of leukemic stem cells in the bone marrow. Seeking to overcome this, Biondi et al expressed the homing receptor CXCR4 in CD33.CAR-cytokine induced killer cells (CIKs) and improved chemotaxis to the bone marrow and increased antileukemic activity. However, expression of the mutant CXCR4 variant associated with WHIM (warts, hypogammaglobulinemia, infections, myelokathexis) syndrome, in which cells are retained in the marrow and display increased homing, did not increase antileukemic efficacy as had been hypothesized, suggesting that CXCR4 acts to amplify killing by another mechanism.
How I treat older patients with DLBCL in the frontline setting
Using 2 illustrative cases, Lugtenburg and Mutsaers review their approach to diffuse large B-cell lymphoma (DLBCL) in older patients. DLBCL is curable but occurs commonly in older individuals with other medical issues that may be an impediment to chemotherapy. Based on a simplified geriatric assessment, the authors discuss the role of full-dose therapy with cytokine support, lower dose therapy, and supportive care in the management of these patients.
Metabolism in stem cell–driven leukemia: parallels between hematopoiesis and immunity
Rattigan and colleagues examine the current understanding of the role of metabolism in proliferation and survival of cancer cells. The authors review the multiple metabolic pathways beyond the “Warburg effect” that impinge on and are modified by leukemia cells. They discuss the degree with which these pathways are shared with normal hematopoietic stem cells and investigate the challenge to discover safe entry points for exploiting metabolic dependence to promote successful therapy without negatively affecting normal hematopoietic stem cells and immune cells.
Targeting the immune microenvironment in Waldenström macroglobulinemia via halting the CD40/CD40-ligand axis
There is increasing attention focused on the immune microenvironment of lymphoid malignancies that appears to protect tumor cells from immune attack. Sacco and colleagues address this question in Waldenström macroglobulinemia (WM). Transcriptomic profiling in a murine model of WM with confirmation in patient samples demonstrated increased regulatory T (Treg) cells with a characteristic signature that is induced and expanded in WM. The authors further identified crosstalk between WM cells and Tregs supported by CD40/CD40 ligand, identifying a potential clinical target for inhibiting WM growth.
