Assessing Time to Diagnosis, End-Organ Damage and Treatment Response in Young Newly Diagnosed Multiple Myeloma Patients

Introduction Multiple myeloma (MM) primarily affects older adults, with a median age of 69 years at time of diagnosis. Presenting symptoms of MM are often vague and nonspecific, such as fatigue or musculoskeletal pain, which can delay diagnosis. This may result in irreversible end-organ damage caused by MM, notably renal insufficiency and lytic bone lesions resulting in pathologic fractures, in addition to the reversible anemia and hypercalcemia that are hallmarks of the disease. Those younger than age 50 represent only 5% of patients living with MM. Though they remain in the minority, the incidence in young patients is rising. Data regarding initial presentation, cytogenetics, and rates of end-organ damage are poorly described, and most information arises from individual case reports or small series. In this study, we performed a retrospective analysis of newly diagnosed MM patients at the age of 51 or younger to characterize this distinct population.

Methods Patients were identified using automated data capture techniques and manually reviewed. All treatment-eligible patients with MM presenting to UC Davis Medical Center between January 2014 to July 2021 were assessed, regardless of diagnosis date. The diagnosis of multiple myeloma was established according to the IMWG criteria, and patients < 51 years were included. Exclusion criteria included patients with non-histologically confirmed MM. Time of symptom onset was defined as the first medical evaluation with documentation of symptoms or radiographic/laboratory abnormalities which could be ascribed to MM as ascertained through chart review. Baseline diabetes, hypertension and coronary artery disease (comorbidities) were tabulated. Myeloma-related complications were defined as hypercalcemia (serum calcium >11 mg/dL), renal insufficiency (serum creatinine >2mg/dL), anemia (hemoglobin <10g/dL), and bone lesions (one or more osteolytic lesion on skeletal radiography, CT, PET/CT, or MRI) at time of diagnosis.

Results 123 patients were included in the study, and their baseline demographics are described in Table 1. The median age was 46.0 years, with a range from 27.8 to 50.9 years; 19 (15%) were age <40. Hypertension was seen in 27 (22%) patients, 7 (5.7%) had diabetes while 93 (74%) had no comorbidities. The most common presenting symptom was musculoskeletal pain 79% of patients. Other presenting manifestations included anemia (13%), fatigue (12%), bacterial infections (8.9%), and weight loss (5.7%). The median time from symptom onset to diagnosis was 1.47 months, with a range of 0 to 49.7 months. Clinical characteristics at diagnosis are described in Table 2. Among the 79 patients with R-ISS staging, 18% had R-ISS Stage I, 70% had Stage II, and 13% had Stage III. Of the 105 patients with cytogenetics data, 19% were high-risk, del(17p) , t(4;14), and/or t(14;16), while 20% had a +1q.

For myeloma-related complications, 14 (11%) had hypercalcemia, 16 (13%) renal insufficiency, and 41 (33%) anemia, 95 (77%) of patients had lytic lesions, and 62 (50%) patients presented with fractures. Of these, 31 had spinal compression fractures, 12 had extra-axial pathologic fractures, and 9 had both. Median time from diagnosis to treatment was 0.60 months, with a range of 0 to 23.93 months. The most common induction regimens, received by 64 (52%) of patients, were immunomodulatory drug and proteasome inhibitor combinations. This is followed by CyBorD (20 patients, 16%) and doublet or other therapy (39 patients, 32%). Autologous stem cell transplantation was utilized by 89 (71%) patients, with 19 (15%) receiving a second transplant. The median age at first transplant was 45.7 years, and 49.8 years at second transplant.

Conclusion We describe one of the largest cohorts of MM patients diagnosed under the age of 51. While on average we did not observe a significant delay between symptom onset and diagnosis, there were some notable outliers. The presenting symptoms and rates of end-organ damage were similar to what has previously been described in older cohorts, though fractures were more common. Transplant was more frequently used than the general population. Additional study on this population is needed to better understand treatment patterns and barriers to their care.

Tuscano:Celgene: Research Funding; Genentech: Research Funding; ADC therapeutics: Research Funding; Achrotech: Research Funding; Takeda: Research Funding; Pharmacyclics: Research Funding; BMS: Research Funding. Abedi:AbbVie: Speakers Bureau; Kite, a Gilead Company: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Celgene: Consultancy, Speakers Bureau; CytoDyn: Current equity holder in publicly-traded company; Orca Bio: Research Funding. Jonas:AbbVie: Consultancy, Other: Travel Reimbursement, Research Funding; GlycoMimetics: Consultancy, Other: protocol steering committee , Research Funding; Gilead: Consultancy, Other: data monitoring committee , Research Funding; 47: Research Funding; Pfizer: Consultancy, Research Funding; Jazz: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Servier: Consultancy; Takeda: Consultancy; Tolero: Consultancy; Treadwell: Consultancy; Accelerated Medical Diagnostics: Research Funding; Amgen: Research Funding; AROG: Research Funding; BMS: Consultancy, Research Funding; Celgene: Research Funding; Daiichi Sankyo: Research Funding; F. Hoffmann-La Roche: Research Funding; Forma: Research Funding; Roche: Research Funding; Hanmi: Research Funding; Immune-Onc: Research Funding; Incyte: Research Funding; Loxo Oncology: Research Funding; LP Therapeutics: Research Funding; Pharmacyclics: Research Funding; Sigma Tau: Research Funding. Kaesberg:Incyte Pharmaceuticals: Honoraria. Rosenberg:Takeda: Other: Institutional Research; Kangpu: Other: Institutional Research; Bristol Myers Squib: Research Funding; Adaptive: Consultancy; Janssen, Takeda: Speakers Bureau.