Sung-Hyun Kim

Background: Toxicity‐related treatment cessation (TTC) limits optimal outcomes in newly diagnosed multiple myeloma (NDMM), but its determinants and prognostic relevance remain unclear. Methods: A total of 3095 NDMM patients were enrolled between 2018 and 2024 in the Asia–Pacific and Australia–New Zealand Myeloma and Related Diseases Registries. Baseline features, treatments, and outcomes were analyzed to identify predictors of TTC and assess its association with progression‐free survival (PFS) and overall survival (OS). Results: TTC occurred in 9% of patients. Advanced age and renal function were independent predictors in multivariable logistic regression, whereas comorbidity burden was not significant after adjustment. Proteasome inhibitor exposure was associated with lower odds of TTC, while immunomodulatory drug use was not independently associated. Patients with TTC had inferior unadjusted survival (median PFS 22.1 vs. 34.4 months; median OS 53.8 vs. 70.8 months; both p < 0.001). In adjusted analyses, TTC was not associated with PFS or OS; however, in age‐stratified analyses, TTC remained associated with shorter PFS in patients aged < 70 years (adjusted HR 1.44, p = 0.03), with no significant association observed in patients ≥ 70 years. Conclusion: TTC may reflect physiologic vulnerability and retains prognostic relevance in younger patients. It may serve as a practical marker to complement frailty assessment in NDMM.

Background: Second salvage autologous stem cell transplantation (SAT) is a therapeutic option for patients with multiple myeloma (MM) who relapse after a first autologous stem cell transplantation (ASCT) in the era of novel agents. However, the clinical context in which SAT provides benefit relative to contemporary salvage regimens remains unclear. Methods: We retrospectively analyzed 51 patients who underwent SAT after novel agent-based induction and first ASCT, and salvage re-induction, and compared outcomes with 113 patients treated with salvage carfilzomib–lenalidomide–dexamethasone (KRd) without SAT. Results: Median interval from first ASCT to relapse was 27 months. In the SAT cohort, median progression-free survival (PFS) and overall survival (OS) from initiation of salvage therapy were 30 and 99 months, respectively. A time to relapse ≥18 months after first ASCT and receipt of SAT as second-line of therapy were associated with significantly longer PFS and OS. In multivariate analysis, administration of SAT at later lines was independently associated with inferior outcomes, while a time to relapse ≥18 months after first ASCT was associated with significantly longer OS. Compared with the KRd-only cohort, SAT was associated with longer OS, whereas PFS was numerically longer without statistical significance. Among patients who had received both a proteasome inhibitor and an immunomodulatory drug as salvage induction, SAT was associated with longer PFS and OS. Conclusions: SAT may provide clinical benefit in selected patients with MM, particularly those with a durable response to first ASCT and those undergoing SAT at an earlier line of relapse in the novel agent era.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed to investigate this regimen’s efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age, 63 years). The overall response rate was 90% in response-evaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, high-risk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2-3 months prior to start of KRd treatment significantly decreased PFS and OS in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e., delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AE) were observed in 56% of the patients, and non-fatal or fatal AE that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large, real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Kim JS, et al. J Korean Med Sci. 2023 Sep;38:e328. https://doi.org/10.3346/jkms.2023.38.e328

Background: With the development of immunology, immune checkpoint inhibitors (ICIs) have been widely used in various cancer treatments. Although some patients can benefit from ICIs, other patients have no response to ICIs or suffer from hyperprogression. There has been no biomarker for predicting the efficacy of ICIs. Thus, the objective of this study was to find biomarkers for predicting the efficacy of ICIs using peripheral blood. Methods: Adults patients planned to be treated with ICIs were enrolled in this study. Blood sampling was carried out before and after administration of ICIs. Changes of immune cell fraction were analyzed for each patient. Results: Among 182 patients enrolled, immune cell analysis was performed for 90 patients. The objective response rate was 14.4% (n = 13/90). The median progression-free survival (PFS) was 6.0 months (95% CI: 3.1–8.9 months), and the median overall survival (OS) was 13.9 months (95% CI: 5.6–22.2 months). Significant benefits in ORR and OS were shown for patients with increased NKp46-/CD56+ NK cells (p = 0.033 and p = 0.013, respectively). The PFS tended to be longer in these patients, although the difference was not statistically significant (p = 0.050). Conclusion: Changes of immune cell fraction before and after administration of ICIs could be a novel biomarker for predicting the efficacy of immunotherapy.

Junshik Hong, Seo-Yeon Ahn, Yoo Jin Lee, Ji Hyun Lee, Jung Woo Han, Kyoung Ha Kim, Ho-Young Yhim, Seung-Hyun Nam, Hee-Jin Kim, Jaewoo Song, Sung-Hyun Kim, Soo-Mee Bang, Jin Seok Kim, Yeung-Chul Mun, Sung Hwa Bae, Hyun Kyung Kim, Seongsoo Jang, Rojin Park, Hyoung Soo Choi, Inho Kim, Doyeun Oh; on behalf of the Korean Society of Hematology Thrombosis and Hemostasis Working Party. Blood Res 2021;56:6-16. https://doi.org/10.5045/br.2021.2020083

Carfilzomib, lenalidomide, and dexamethasone (KRd) effectively improve survival in patients with relapsed and refractory multiple myeloma (RRMM). However, the outcome of KRd treatment in Asian patients reflecting a general RRMM population outside of a clinical trial has not been reported. Fifty-five RRMM patients who were treated with carfilzomib in combination with Rd from the time of the first approval of KRd in the Republic of Korea were analyzed. The median age was 61 years. The percentage of patients with an ECOG performance status ≥ 3, creatinine clearance < 50 mL/min, high-risk cytogenetics, and ≥ 4 lines of prior treatment were 9%, 22%, 31%, and 27%, respectively. Forty-one patients started treatment with KRd, whereas the remaining 14 patients (25%) were added carfilzomib during the Rd treatment. In the whole cohort, the overall response rate was 73% and progression-free survival was 8.8 months. The addition of carfilzomib in patients who were refractory or had disease progression during Rd treatment reattained a response in half of the patients. The advantage of carfilzomib with Rd was significant in patients in the first relapse. Toxicity profile was acceptable, excluding severe infections. Carfilzomib in combination with Rd is effective and has a reasonable adverse event rate in Asian patients with RRMM.

Ji Hyun Lee, Sung-Hyun Kim. Blood Res 2020;55:S43-53. https://doi.org/10.5045/br.2020.S008

Background The recent discontinuation clinical trials have demonstrated that IM discontinuation can be employed based on clinical study in patients who had enough IM therapy and undetectable molecular residual disease (UMRD) durations prior to IM discontinuation. Moreover, treatment rechallenge in patients with molecular recurrence lead a second deep molecular response, suggesting that IM discontinuation is safe. However, the issues on the definition of molecular relapse requiring treatment resumption and the occurrence of late relapse with a long-term follow-up after IM discontinuation are important. Therefore, here we analyzed the long-term follow-up results of the patients who lost UMRD after IM discontinuation Methods CP CML patients who were treated with IM for more than 3 years and had undetectable levels of BCR-ABL1 transcripts determined by quantitative reverse transcriptase polymerase chain reaction (PCR) for at least 2 years were eligible for KID study and in cases of MMR loss after 2 consecutive assessments, IM treatment was re-introduced. After IM resumption for MMR loss, the molecular response was evaluated every month until MMR was re-achieved and every 3 months thereafter. The second stop was permitted in the patients who were in second UMRD for at least 2 years. Results Between October 2010 and June 2015, a total of 126 patients (70 females, 56 males) were enrolled on KID Study, with a median age of 47 years (range, 18-82), the percentages of patients with low, intermediate and high Sokal risk scores were 33%, 25% and 15%, respectively with unknown Sokal risk scores in 27%. And the median time on IM therapy and the median duration of sustained UMRD prior to discontinuation were 83 months (range, 32-141) and 41 months (range, 22-131), respectively. After a median follow-up of 62.6 months (range, 4.9-100.8 months) after IM discontinuation, 83 patients (65.9%) lost UMRD. Among them, 56 (67.5%) patients lost MMR in 2 consecutive analyses. The other 27 (32.5%) patients who lost UMRD but not MMR exhibited different patterns of BCR-ABL1 kinetics: 8 patients spontaneously re-achieved UMRD after a median time of 2.8 months (range, 0.9-3.0 months), and 19 patient showed fluctuation of BCR-ABL1 transcript under the level of 0.1% on IS for a median 19 months (range, 3-34), and then spontaneously returned and maintained UMRD for a median 31 months (range, 2-64). Of 73 patients who lost MR^4.0, the rate of MMR loss was 76.7%. Out of 56 patients with molecular relapse, 54 patients (except two patients who restart radotinib) were re-treated with IM, all patients (except one patient lost follow-up) re-achieved MMR at a median of 1.9 months (range, 0.0 - 5.4 months) after resuming treatment. Among them, two patients who re-achieving of MMR after resuming IM therapy lost MMR again; One patient who relapsed at 53.2 months after IM discontinuation, despite re-achieving MMR 1.4 later after IM restarting, suddenly progressed to blast crisis at 6 months after restarting IM and in spite of switching to dasatinib and ponatinib, she died. Another patient lost MMR at 7.4 months after IM discontinuation and re-achieved MMR 1.7 later after IM restarting, but progressed to AP on the assessment 32 months later. The patient switched to dasatinib and lost follow-up. Among the patients who maintained a second UMRD for at least 2 years after IM resumption, 23 patients entered into a second IM stop. With a median follow-up of 29.5 months (range, 9-63 months) since second IM stop, 15/23 patients (65%) lost MMR after a median 2.9 months (range, 1.8-30.7 months), which was similar to those of the first IM discontinuation [median 3.7 (range, 1.8-20.8 months)]. The patients who lost MMR were retreated with IM for a median of 24.5 months (range, 1.2-49.7 months); 14 patients re-achieved MMR and one patient was in therapy for 1.2 months. Conclusions Our results showed that 67.5% and 76.7% of patients who lost UMRD and MR^4.0, respectively resulted in MMR loss, and the other patients were below MMR without re-treatment, suggesting loss of MMR can be chosen for treatment re-challenge. Overall, IM discontinuation could be applied with approximately 55% of probability of sustained MMR in the long term. In addition, we demonstrated that a second attempt might be possible. Further studies on the predictors to select patients for a trial of second stop are warranted.