Multiple Myeloma and Pulmonary Hypertension: What Is the Connection?

Introduction: While increased prevalence of pulmonary hypertension (PH) has been shown consistently in multiple myeloma (MM), there is limited evidence on progression of disease or disease-related indicators in this population. Multiple factors related to MM can contribute to the development of PH, including cardiac and renal disease, high output states, a prothrombotic state, amyloidosis, and vasculopathy, though the complex pathophysiology underlying this remains poorly understood.

Methods: A retrospective chart review of all patients diagnosed with MM and PH from 2013-2023 was performed at our single academic center. International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes were used to select patients. Exclusion criteria included having a hematologic malignancy other than MM, diagnosis of a secondary malignancy, lack of presenting MM diagnostic data (hemoglobin, creatinine, calcium, albumin, and lactate dehydrogenase (LDH), lack of necessary echocardiographic data, and right ventricular systolic pressure on echocardiography of <40mmHg. Of 4,101 patients with MM, 48 (1.17%) had an ICD-10-CM diagnosis of pulmonary hypertension. Thirty patients met inclusion criteria and were compared to 28 age- and gender-matched controls with MM but no PH by echocardiography.

Results: At the time of MM diagnosis, there was no statistically significant difference in age (study group (SG)= 71.76 years old; control group (CG) = 71.87 years old; p-value 0.852) or gender (SG= 33.3% male, 66.7% female; CG= 35.7% male, 64.3% female; p-value 0.849). There were similar rates of known common causes of pulmonary hypertension: Left Heart Disease (17/30 [57%] in SG vs 15/28 [54%] in CG); connective tissue diseases (4/30 [13%] in SG vs 0/28 in CG); Cirrhosis (1/30 [3%] in SG vs 0/28 in CG); ESRD (1/30 [3%] in SG vs 1/28 [4%] in CG); Methamphetamine use (0/30 in SG vs 0/28 in CG). At the time of MM diagnosis, there was a statistically significant difference in presenting hemoglobin (SG=10.74; CG=11.42; p-value 0.049), albumin-corrected calcium (SG=10.54; CG=9.52; p-value 0.024), and creatinine (SG=1.31; CG= 1.73; p-value 0.017). There was no statistically significant difference in unadjusted calcium (SG=9.97; CG= 9.52; p-value 0.265), or LDH (SG=252.62; CG=166.55; p-value 0.171). High risk cytogenetic abnormalities including del(17p), t(4;14) or t(14;16) were not statistically significant between groups, though there were 3 patients in the SG without initial cytogenetics. There was no significant difference between the number of treatment lines used or stem cell transplantation between groups. Treatment at any time in the disease course with immunomodulatory agents occurred more often in the CG, 28/28, compared to the SG, 24/30; p 0.024.

Conclusions: Lower baseline hemoglobin and higher corrected calcium at initial diagnosis of MM was seen in patients who developed PH when compared to patients who did not develop PH after MM diagnosis. Higher creatinine levels in the control population could indicate a distinct mechanism driving renal versus pulmonary involvement of MM. High-risk cytogenetic abnormalities did not differ between groups, but more investigation into overall cytogenetic differences is needed to confirm this. Use of immunomodulatory agents was surprisingly higher in the control population, suggesting therapy-related pulmonary hypertension is not driving this process. When determining which patients should undergo early screening, it is helpful to recognize that differences in myeloma defining factors, such as a higher degree of anemia and less severe renal disease at diagnosis, may delineate a population more likely to develop pulmonary hypertension.

No relevant conflicts of interest to declare.