Patterns of relapse and progression in multiple myeloma patients after auto-SCT: implications for patients’ monitoring after transplantation

Abstract

Autologous stem cell transplantation (ASCT) is widely used in first-line treatment of multiple myeloma (MM). However, most patients eventually have relapse or progression of disease (R/POD). While precise knowledge of R/POD patterns would be important to generate evidence-based surveillance recommendations after ASCT, such data is limited in the literature, especially after introduction of the free light chain assay (FLCA). This retrospective study examined the patterns of R/POD after first-line ASCT in 273 patients, using established criteria. At time of R/POD, only 2% of patients had no associated serologic evidence of R/POD. Eighty five percent had asymptomatic R/POD first detected by serologic testing, while 15% had symptomatic R/POD with aggressive disease, early R/POD, and short survival, with poor cytogenetics and younger age identified as risk factors. While occult skeletal lesions were found in 40% of asymptomatic patients tested following serologic R/POD, yearly skeletal surveys and urine testing were poor at heralding R/POD. We found a consistent association between paraprotein types at diagnosis and R/POD allowing informed recommendations for appropriate serologic monitoring and propose a new needed criterion using FLCA for patients relapsing by FLC only. Our findings provide important evidence-based recommendations that strengthen current monitoring guidelines after first-line ASCT in MM.

Pattern of relapse and progression after autologous SCT as upfront treatment for multiple myeloma

“…7 The relapse pattern on the 'transformed' disease, such as plasmablastic myeloma of secondary plasma cell leukemia, was very rare in our series in comparison with previous reports, 7,20 but was in agreement with a recent study. 18 As previously reported, the recognized dismal prognostic impact of EMP at diagnosis in patients treated with conventional chemotherapy can be overcome with the use of high-dose chemotherapy. 19,22 Of interest, the presence of this complication at relapse/progression was not significantly associated with a shortened survival in the present study.…”

“…Light-chain urine protein measurements at relapse/progression were crucial, particularly in patients with M-spike in the urine at diagnosis. In contrast to some recent observations, 18 sequential measurement is very helpful and we strongly recommend that the 24-h-urine light-chain protein excretion is measured at each visit, particularly in patients who had light chains in the urine at presentation. The pattern of the urine M-component was variable, with some patients showing a more indolent behavior, and others showing a very quick increase.…”

“…This pattern has received several names, such as insidious 20 or asymptomatic 18 form, in comparison with the symptomatic classical pattern, characterized by anemia, new osteolytic lesions, hypercalcemia, renal failure, EMP, plasma cell leukemia or plasmablastic/lymphoma like. Commonly, relapsed patients respond to conventional chemotherapy such as melphalan-or steroid-based regimens.…”

Zoledronic acid as compared with observation in multiple myeloma patients at biochemical relapse: results of the randomized AZABACHE Spanish trial

“…First, biochemical relapses are very frequent. 25,26 Second, most patients who have biochemical relapses very soon require therapy; Fernandez-Larrea et al recently reported that most such patients need therapy at a median time of 5.6 months after transplantation, 27 which is concordant with the estimations from the VISTA trial in non-transplant candidates upon comparing time to progression and TNT.28 Third, there is no universal consensus on how to treat these patients and many physicians prefer not to treat until symptoms emerge. …”

Clinical course and outcomes of patients with multiple myeloma who relapse after autologous stem cell therapy

“…4 However, the clinical outcomes amongst such patients are quite heterogeneous and very few studies have documented their clinical course and subsequent therapies received. [5][6][7] We specifically analyzed the Prog-OS for patients undergoing early or delayed ASCT separately. This was because patients undergoing a delayed ASCT would have relapsed with more chemotherapy exposure and thus more likely to have a more aggressive disease course upon relapse.…”