Novel agent mitigates effects of pyruvate kinase deficiency

Mitapivat significantly increases haemoglobin levels, decreases haemolysis, and improves patient-reported outcomes in adults with pyruvate kinase deficiency, a study shows.

A phase 3 RCT in 80 patients found a haemoglobin response in 40% of those randomised to the first-in-class, oral, allosteric activator of red-cell pyruvate kinase for 24 weeks versus 0% of placebo controls (p<0.001).

In secondary endpoints, patients who received mitapivat also had a greater response than controls across markers of haemolysis (the indirect bilirubin, LDH, and haptoglobin levels) and haematopoietic activity (the reticulocyte percentage).

Adverse events of grade 3 or higher occurred in 25% of the mitapivat-treated patients compared to 13% of the controls. The most common AEs in the mitapivat group were hypertriglyceridemia and hypertension.

Eligible participants had at least two mutant alleles in PKLR, of which at least one was a missense mutation.

“…the results hold promise that chronic, lifelong haemolytic anaemia in patients with pyruvate kinase deficiency, and its consequent negative effect on health-related quality of life, may be averted in patients with pyruvate kinase deficiency of certain genotype,” the study authors said.

Read more in The NEJM

Bispecific antibody shows promise in RR follicular lymphoma

Mosunetuzumab induces deep and durable remissions in patients with relapsed/refractory follicular lymphoma who have received ≥2 prior lines of therapy.

A phase 11 international study, including Australians, found the CD20xCD3 bispecific antibody led to a best objective response rate (ORR) of 78.9% and complete response (CR) rate of 57.8%.

Best ORR and CR were consistent in prespecified subgroups including patients with two prior lines of therapy, three or more lines of therapy, disease refractory to prior anti-CD20 antibody therapy, double refractory disease and progression of disease within 24 months of initial therapy.

The most common adverse event was cytokine release syndrome (44.4%), most of which were low grade and resolved after a median of three days.

Other common AEs included fatigue (36.7%), headache (31.1%), neutropenia and pyrexia (28.9% each), hypophosphataemia (22.2%) and pruritus (21.1%).

The results were presented at the 62nd ASM of the British Society for Haematology.

Fear of recurrence is widespread among cancer survivors

More than half of cancer survivors have a significant fear of cancer recurrence, and for about one in five the anxiety is severe enough to warrant specialist intervention, a study has found.

A meta-analysis of individual participant data for more than 9300 cancer patients and survivors found that 59% report at least a moderate level of fear of cancer recurrence and 19% experience a high level.

Fear of cancer recurrence was more prevalent among female and younger patients, and highest scores were reported for people with lung cancer and melanoma, whereas participants with prostate cancer reported the lowest scores;

“We recommend providing brief psycho‐education about fear of cancer recurrence to all cancer survivors and patients, to normalise fear of cancer recurrence and help individuals seek support when they need it, even if they are no longer undergoing hospital‐based treatment or surveillance,” the study said.

Read more in Psycho-Oncology.