AF Common, Worsens Prognosis After Stem Cell Transplant for Multiple Myeloma

Atrial fibrillation (AF) is a relatively frequent complication after autologous stem cell transplantation in patients with multiple myeloma, one that’s associated with an increased risk of mortality, a retrospective study shows.

Factors associated with posttransplant AF in this population include age > 65 years, a history of paroxysmal AF, and obesity, lead author Olayiwola Bolaji, MD (Memorial Sloan Kettering Cancer Center, New York, NY), and colleagues report in a paper published recently in JACC: CardioOncology.

The study “really reinforces the absolute need to focus on these patients for cardiovascular assessment and surveillance before, during, and after a transplant,” senior author Jennifer Liu, MD (Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, NY), told TCTMD.

Although autologous stem cell transplantation is a cornerstone therapy for multiple myeloma, “the procedure places significant physiologic stress on patients,” she explained. “And because atrial fibrillation is the most common cardiovascular complication during cancer treatment, we wanted to understand how often A-fib occurs after transplant, who develops it, and, more importantly, how it affects outcomes.”

The retrospective study included 801 patients with multiple myeloma (median age 62 years; 41.3% women) who underwent autologous stem cell transplantation at Memorial Sloan Kettering Cancer Center between 2016 and 2022. A pretransplant CV evaluation involved ECG and echocardiography performed within 180 days of conditioning chemotherapy.

Through a median follow-up of 36.2 months, 8.7% of patients developed posttransplantation AF, with cumulative incidences of 5.5% at 90 days and 9.0% at 3 years. The median interval between transplant and the development of AF was 13 days.

After multivariable adjustment, three factors were significantly associated with development of AF: a history of paroxysmal AF (HR 6.19; 95% CI 3.63-10.5), obesity (HR 2.00; 95% CI 1.10-3.63), and age > 65 years (HR 1.88; 95% CI 1.16-3.07). When patients with a history of AF were excluded, having a corrected QT interval > 480 ms also was associated with AF.

‘Systemic Vulnerability’

One of the most important findings, according to Liu, was the prognostic impact of posttransplant AF. It was associated with both all-cause mortality (HR 5.05; 95% CI 3.05-8.37) and nonrelapse mortality (HR 4.53; 95% CI 1.43-14.30).

The mechanism that explains the relationship with mortality remains unclear, but the study “suggests that A-fib is not simply a periprocedural complication but really reflects underlying systemic vulnerability,” Liu said.

The procedure places significant physiologic stress on patients. Jennifer Liu

Salim Hayek, MD (University of Texas Medical Branch, Galveston), and Mary Riwes, DO (University of Michigan, Ann Arbor), pick up a similar thread in an accompanying editorial, saying that the link between posttransplant AF and mortality, driven by nonrelapse deaths and not those related to myeloma progression, “reframes AF from a cardiac endpoint to a systemic prognostic indicator, identifying patients with challenged cardiovascular reserve.”

The concept of posttransplant AF as a marker of systemic vulnerability also is supported, they argue, by the low rate of stroke during follow-up (2.9% among patients with AF) and by the fact that AF “frequently occurred in the context of sepsis, respiratory decompensation, or without identifiable triggers, suggesting that the arrhythmia develops as a manifestation of broader physiological stress rather than as an isolated cardiac event.”

Hayek and Riwes acknowledge, however, that definitive conclusions cannot be drawn from this study due to its retrospective design and the lack of detailed information on causes of death.

There are a number of questions that need to be answered in future research, Liu said, including whether intervening early with rhythm control or implementing preventive strategies to stave off posttransplant AF can improve outcomes.

For now, Liu said, these findings underscore the need for a CV evaluation in this patient population. “The cardio-oncology guidelines recommend that all patients undergoing potentially cardiotoxic treatment should have a comprehensive cardiovascular assessment before transplant, followed by a risk-stratifying, monitoring approach,” she explained.

These patients often have high CV risk going into the procedure, so “it’s even more imperative in this particular scenario that they have a comprehensive cardiovascular assessment and risk factor optimization,” Liu said.