Posttreatment M‐Protein Nadir Level Is a Significant Prognostic Factor Associated with Survival in Multiple Myeloma

Shimizu, Kazuyuki; Kamiya, O; Hirabayashi, N; Ichikawa, Atsushi; Kawashima, Kohei; Kobayashi, Masahide; Mizuno, Harumitsu; Nagura, Eiichi; Nitta, Masakazu; Saito, Hidehiko; Sao, Hiroshi; Shibata, Toshihiko; Takeyama, Hideo

doi:10.1111/j.1349-7006.1999.tb00755.x

Cited by 4 publications

(5 citation statements)

References 10 publications

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“…They also found that established prognostic parameters, including Salmon & Durie stage, serum creatinine, and hemoglobin, remained significant, leading to the conclusion that early response to MP treatment predicted for survival in multiple myeloma. However, in 2 retrospective studies by Shimizu et al, also in the frontline setting, the post-treatment nadir in M protein level was prognostic for survival outcome, but the percentage fall in M protein was not prognostic 8, 9 . Moreover, van Rhee et al have reported that a rapid reduction in myeloma burden, as measured by a top-tertile reduction in the serum-free light chain levels before cycle 2, predicted for an inferior progression-free and 2-year overall survival after their induction therapy and tandem transplantation approach 10 .…”

Section: Discussionmentioning

confidence: 90%

Rapid early monoclonal protein reduction after therapy with bortezomib or bortezomib and pegylated liposomal doxorubicin in relapsed/refractory myeloma is associated with a longer time to progression

Shah

Bladé

Sonneveld

et al. 2011

Cancer

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Background A rapid and early monoclonal (M) protein response during initial therapy in patients with multiple myeloma has been identified as a predictor of superior long-term outcome in some, but not all studies. Methods To determine if the parameter of M protein reduction was of value in the relapsed and/or refractory setting, we performed a retrospective landmark analysis at the end of cycles 2 and 4 of a phase III study which randomized such patients to receive bortezomib alone, or pegylated liposomal doxorubicin (PLD) with bortezomib. Results: Compared with a <25% reduction in M protein at the landmark time point, patients with a 50-<75% reduction after cycle 2 had a significantly lower hazard ratio for time to progression [hazard ratio (HR)=0.41; 95% confidence interval [CI] (0.26, 0.64); P<.001], as did those with a ≥75% reduction [HR=0.26; 95% CI (0.15, 0.45); P<.001]. In all of these groups, PLD + bortezomib provided superior outcomes to bortezomib alone, and did so without an increase in the risk of adverse events overall and a predictable toxicity profile. Conclusions These analyses support the possibility that a robust early M protein response is a good prognostic factor for long-term outcome of myeloma patients with relapsed and/or refractory disease receiving bortezomib or PLD + bortezomib.

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Section: Discussionmentioning

confidence: 90%

Rapid early monoclonal protein reduction after therapy with bortezomib or bortezomib and pegylated liposomal doxorubicin in relapsed/refractory myeloma is associated with a longer time to progression

Shah

Bladé

Sonneveld

et al. 2011

Cancer

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“…12 Dispenzieri et al 13 demonstrated the utility of FLC after 2 months of therapy to predict the overall response. Furthermore, several other studies have shown retrospective association between FLC/M-protein reduction and the long-term benefit, such as progression-free survival (PFS) or overall survival, [13][14][15][16][17][18] which is critical for predicting antitumor activities for new agents and personalizing therapy for patients with myeloma.…”

Section: Study Highlightsmentioning

confidence: 99%

“…To date, the retrospective studies of the association between M-protein dynamics and PFS or overall survival have been mainly based on complete M-protein dynamic data collected up to the time of disease progression. [13][14][15][16][17][18] Therefore, the prospective ability of M-protein, particularly early measurements within 2-3 months of therapy, to predict long-term survivals remains unknown. Moreover, because most of existing association studies were performed based on nonrandomized, single-arm phase II studies, [13][14][15]17,19 translation of the significant association between M-protein and survival in these studies to treatment effects compared with control arms in the randomized phase III studies is still challenging.…”

Section: Study Highlightsmentioning

confidence: 99%

“…To date, the retrospective studies of the association between M‐protein dynamics and PFS or overall survival have been mainly based on complete M‐protein dynamic data collected up to the time of disease progression 13–18 . Therefore, the prospective ability of M‐protein, particularly early measurements within 2–3 months of therapy, to predict long‐term survivals remains unknown.…”

mentioning

confidence: 99%

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Early M‐Protein Dynamics Predicts Progression‐Free Survival in Patients With Relapsed/Refractory Multiple Myeloma

Yan

Weisel

et al. 2020

Clinical Translational Sci

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This study aimed to predict long-term progression-free survival (PFS) using early M-protein dynamic measurements in patients with relapsed/refractory multiple myeloma (MM). The PFS was modeled based on dynamic M-protein data from two phase III studies, POLLUX and CASTOR, which included 569 and 498 patients with relapsed/refractory MM, respectively. Both studies compared active controls (lenalidomide and dexamethasone, and bortezomib and dexamethasone, respectively) alone vs. in combination with daratumumab. Three M-protein dynamic features from the longitudinal M-protein data were evaluated up to different time cutoffs (1, 2, 3, and 6 months). The abilities of early M-protein dynamic measurements to predict the PFS were evaluated using Cox proportional hazards survival models. Both univariate and multivariable analyses suggest that maximum reduction of M-protein (i.e., depth of response) was the most predictive of PFS. Despite the statistical significance, the baseline covariates provided very limited predictive value regarding the treatment effect of daratumumab. However, M-protein dynamic features obtained within the first 2 months reasonably predicted PFS and the associated treatment effect of daratumumab. Specifically, the areas under the time-varying receiver operating characteristic curves for the model with the first 2 months of M-protein dynamic data were ~ 0.8 and 0.85 for POLLUX and CASTOR, respectively. Early M-protein data within the first 2 months can provide a prospective and reasonable prediction of future long-term clinical benefit for patients with MM. Daratumumab is a human immunoglobulin G (IgGκ) monoclonal antibody that targets CD38 and kills malignant plasma cells via direct antitumor and immunomodulatory mechanisms of action. 1-7 Daratumumab induces antitumor activity through several CD38 immune-mediated actions, including complement-dependent cytotoxicity,

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“…Shimizu ve arkadaşlarının yaptığı 2 retrospektif çalışmada, tedavi sonrası en düşük M protein seviyeleri pronoz ve sağkalım ile ilişkili bulunmuş ama M protein yüzde düşüşleri prognostik bulunmamıştır (3,4). Blade ve arkadaşlarının yaptığı çalışmada sadece tedaviye cevabın sağkalımı etkilediği sonucuna ulaşmıştır (5).…”

Section: Tartişma Ve Sonuçunclassified

Is the Decrease in the Immunoglobulin Level Important After First Cycle Chemotheraphy of the Newly Diagnosed Multiple Myeloma Patients?

Akyazı¹,

Kelkitli²,

Turğut³

2019

LLM Dergi

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Is the Decrease in the Immunoglobulin Level Important After First Cycle Chemotheraphy of the Newly Diagnosed Multiple Myeloma Patients? ÖZET Amaç: Multipl miyelom (MM) tek bir klonal plazma hücresinin proliferasyonu sonucu gelişen malign bir hastalıktır. Progresyonu ve nüksü geciktirebilmek tedavilerin ana amacıdır. Tedavilere cevap hastalığın uzun vadeli sonuçlarını etkileyebilir bu cevabı en erken zamanda değerlendirebilmek tedavi stratejilerini belirlemede önem arz etmektedir. Bu çalışmanın amacı, bir kür kemoterapi sonrasında immünoglobulin düzeyindeki azalmanın tedaviye yanıt oranı, progresyonsuz sağkalım (PFS) ve genel sağkalım ile ilişkisini araştırmaktır.Hastalar ve Yöntem: Çalışmamızda kliniğimizde Ocak 2007-Şubat 2016 tarihleri arasında yeni tanı almış, tedavi takipleri merkezimizde yapılmış 153 MM hastası retrospektif olarak değerlendirildi. Hastaların tedavileri, tedaviye yanıtları, ortalama sağkalım ve progresyonsuz sağkalım süreleri belirlendi. Tanı anındaki immünoglobülin değerleri ile birinci kür sonundaki immünoglobulin değerleri arasındaki fark belirlendi. Bu oranlar tedaviye yanıt, PFS ve OS ile karşılaştırıldı.Bulgular: İmmünoglobulinler'de ilk kür kemoterapi ile tedavi gruplarından bağımsız olarak yapılan değerlendirmede %50'den fazla düşen hastaların %90'ında çok iyi kısmi yanıt (ÇİKY) görülmüştür. En az ÇİKY alınan hastalarda medyan hastalıksız sağkalım süresi 45 ay iken daha kötü yanıtlar alınan hastalarda medyan hastalıksız sağkalım süresi 12 ay olarak bulundu. Beş yıllık median sağkalım süresi; < %25 azalış oranlarda 29 ay, %25-50 azalış olanlarda 61 ay, %51-75 azalış olanlarda 66 ay, > %75 azalış olanlarda 76 ay olarak bulundu. Sonuç: Biz çalışmamızda ilk kür kemoterapi ile immünoglobulin düşüşünün fazla olmasının yanıt oranları, progresyonsuz sağkalım ve genel sağkalım ile ilişkili olduğu görüldü. Erken paraprotein yanıtı diğer risk belirteçleri gibi tedavi stratejilerinde kullanılabilir ve cevaplara göre tedavi bireyselleştirilebilir.

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Posttreatment M‐Protein Nadir Level Is a Significant Prognostic Factor Associated with Survival in Multiple Myeloma

Cited by 4 publications

References 10 publications

Rapid early monoclonal protein reduction after therapy with bortezomib or bortezomib and pegylated liposomal doxorubicin in relapsed/refractory myeloma is associated with a longer time to progression

Rapid early monoclonal protein reduction after therapy with bortezomib or bortezomib and pegylated liposomal doxorubicin in relapsed/refractory myeloma is associated with a longer time to progression

Early M‐Protein Dynamics Predicts Progression‐Free Survival in Patients With Relapsed/Refractory Multiple Myeloma

Is the Decrease in the Immunoglobulin Level Important After First Cycle Chemotheraphy of the Newly Diagnosed Multiple Myeloma Patients?

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