David Bai, PharmD

Two recent studies analyzed patients with multiple myeloma to identify factors that impacted response to therapy.

Patients who achieve a very good partial response (VGPR) or better have longer progression-free survival (PFS) than patients who have poorer responses to induction therapy. Patients who do not achieve maximum response after 4 cycles of induction therapy should continue induction therapy until maximum response is achieved.

PFS is an important endpoint that for many hematologic malignancies, including multiple myeloma. As one of the primary survival endpoints, it is essential that investigators identify what patient characteristics lead to longer-term responses to improve treatment. In one study, investigators analyzed patients with multiple myeloma to identify any common features that led to longer term responses.

Patients from the UK MRC Myeloma IX (M-IX) and NCRI Myeloma XI (M-XI) trials were studied and separated between long-term response post induction (PFS ≥48 months) and those with PFS <48 months. Patients in the M-IX trial received either alkylating therapy (cyclophosphamide, vincristine, doxorubicin [Adriamycin], dexamethasone [CVAD] or melphalan, prednisone [MP]) or thalidomide-based induction (cyclophosphamide, thalidomide, dexamethasone [CTD]) therapy while patients in the M-XI trial received either thalidomide or lenalidomide-based induction (CTD or cyclophosphamide, lenalidomide [Revlimid], dexamethasone [CRD]) and response-based bortezomib intensification (cyclophosphamide, bortezomib [Velcade], dexamethasone [CVD]).

In both trials, a higher number of transplant-eligible patients had a PFS ≥48 months compared with patients who were ineligible for transplant (M-IX, 25.8% vs 7%, respectively; M-XI, 34.2% vs 10.2%). Longer PFS also translated to longer overall survival in both trials. Factors that were associated with PFS ≥48 months included International Staging System I and lower performance status (WHO). Patients with high-risk lesions (gain [1q] or del[17p]) were more frequently in the PFS <48-month group. In a multivariable analysis of baseline parameters, absence of gain [1q] was the only genetic factor associated with PFS ≥48 months in transplant-ineligible patients. In comparison, absence of all high-risk lesions was associated with PFS ≥48 months in transplant-eligible patients.

Articles

Two recent studies analyzed factors that impacted response to therapy in patients with multiple myeloma. 

What Factors Influence Response to Multiple Myeloma Treatment?

A genetic risk variant, rs7665090G, located near NFKB1, on astrocytes enhances the accessibility of the central nervous system (CNS) to peripheral immune cells, escalating the risk of autoimmune inflammation and multiple sclerosis (MS), according to the results of a recent study.

One recent finding suggested that changes in immune enhancers such as lymphocytes may disrupt innate and adaptive immune pathways; however, investigators were still unsure whether they affected CNS function and thus increased MS risk. In this study, rs7665090G was used to determine whether dysregulation in astrocyte function will affect MS risk.

Nuclear factor-κ—light chain enhancer of activated B cells (NF-κB) is an essential part of innate and adaptive immunity and plays a role in autoimmunity. Changes in NF-κB signaling have been associated with cancer and inflammatory and autoimmune diseases. In this study, investigators compared induced pluripotent stem cells (iPSCs)–derived astrocytes from patients who were healthy and patients with MS who were had a homogenous risk variant (rs7665090GG) or protective variant (rs7665090AA). In unstimulated astrocytes, both groups had low NF-κB signaling. However, once NF-κB signaling was stimulated using tumor necrosis factor α and IL-1β, NF-κB activation was significantly higher in the astrocytes that carried the risk variant.

A version of this article was orginally published by the American Journal of Managed Care. Continue reading the full article at 

Study results show a genetic risk variant on astrocytes enhances the accessibility of the central nervous system (CNS) to peripheral immune cells, escalating the risk of autoimmune inflammation and multiple sclerosis.

Study: Genetic Risk Variant Linked to Astrocytes Increases Risk of MS

Children with Hodgkin lymphoma who are treated during childhood and survive to adulthood have higher incidence rates of breast, lung, colorectal, and thyroid cancer than the general population, according to a recent study.

Hodgkin lymphoma is considered one of the most treatable forms of lymphoma, with many patients surviving more than 5 years. Although Hodgkin lymphoma, especially if diagnosed at an earlier stage, offers good prognosis, previous studies have identified that the risk of solid subsequent malignant neoplasms (sSMNs) are significantly increased. In this study, survivors of Hodgkin lymphoma were followed up beyond 25 years to identify groups with the highest risks of developing sSMNs.

Of the 1136 patients diagnosed with Hodgkin lymphoma, a total of 196 sSMNs developed in 162 patients. The neoplasms included breast cancer in 54 patients, basal cell carcinoma in 34 patients, thyroid cancer in 30 patients, colorectal cancer in 15 patients, lung cancer in 11 patients, other malignancies in 40 patients, and unknown disease site in 12 patients. Cumulative incidence rates of patients with Hodgkin lymphoma for any sSMNs was 26.4% at 40 years after diagnosis, and overall risk was found to be 14 times higher than the general population.

The development of breast cancer occurred mainly in female survivors of Hodgkin lymphoma (42 patients), with incidence rates of 20.1% at 40 years from diagnosis. Identified subgroups at highest risk were females diagnosed with Hodgkin lymphoma between 10 to 16 years old and exposure to chest radiotherapy. Overall risk of developing breast cancer was 25.8 times higher for patients with Hodgkin lymphoma than the general population.

Survivors of Hodgkin Lymphoma have higher incidence rates of breast, lung, colorectal, and thyroid cancer later in life compared with the general population, new study says. 