Impact of maintenance therapy on subsequent treatment in patients with newly diagnosed multiple myeloma: use of "progression-free survival 2" as a clinical trial end-point

Dimopoulos, Meletios Α.; Petrucci, Maria Teresa; Foà, Robin; Catalano, John; Kropff, Martin; Terpos, Evangelos; Grote, Lara; Jacques, Christian; Palumbo, Antônio

doi:10.3324/haematol.2014.120790

Cited by 22 publications

(19 citation statements)

References 12 publications

(14 reference statements)

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“…The proportion of patients receiving bortezomib-based second-line therapy was 53% in the FIRST trial 14 and 31% in the MM-015 trial. 15 Among 543 patients who experienced first progression, 44% had evidence of CRAB criteria, which is similar to our cohort in which a total of 48% were found to have CP with or without EM disease. They demonstrated a significantly lower post-progression OS in patients with morbid relapse compared to those with asymptomatic relapse (median OS, 23 vs 39 months, respectively).…”

Section: Discussionsupporting

confidence: 84%

Progression with clinical features is associated with worse subsequent survival in multiple myeloma

et al. 2019

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Response rate and survival in multiple myeloma (MM) has improved in the era of proteasome inhibitors and immunomodulatory drugs. However, most patients eventually relapse with biochemical progression (BP) alone or with clinical features of end‐organ damage (CP: clinical progression), without or without extramedullary (EM) disease. We conducted a retrospective cohort study of 252 patients with MM experiencing first relapse (time, T0) to evaluate survival following CP with and without EM as a function of BP. Patients were divided into three groups: BP (n = 134; 53%), CP/EM‐ (n = 87; 35%) and CP/EM+ (n = 31; 12%). The median time from diagnosis to T0 was significantly shorter in CP/EM+ compared to CP/EM‐ and BP groups (13 vs 25 vs 25 months; P < 0.001). The incidence of abnormal metaphase cytogenetics at diagnosis was significantly higher in CP/EM+ compared to CP/EM‐ and BP groups (46% vs 18% vs 11% respectively; P < 0.001). At a median follow‐up of 26 months from T0, median overall survival was 50, 19 and 10 months for BP, CP/EM‐ and CP/EM+ groups, respectively (P < 0.001). On multivariable analysis, pattern of progression was a significant prognostic factor for OS (HR for CP/EM‐ vs BP: 3.6; CP/EM+ vs BP: 8.7 and CP/EM+ vs CP/EM‐: 2.42; P < 0.001 for all comparisons), along with age at T0. In conclusion, progression pattern is an important prognostic factor in the current era, with subsequent survival being dismal in patients with end‐organ damage or EM disease at relapse. Clinical trials in relapsed MM should consider reporting patterns of progression at baseline to ensure balance between study arms.

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Section: Discussionsupporting

confidence: 84%

Progression with clinical features is associated with worse subsequent survival in multiple myeloma

et al. 2019

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“…Time from start of treatment to serological or symptomatic progressive disease, or death, whichever occurred first, defined progression‐free survival (PFS). To investigate aggressiveness of 1st relapse and impact of first‐line therapy on future cause of the disease, we also analyzed PFS‐2, as described previously . Patients alive and without disease progression at the time of last follow‐up were censored in the respective analysis.…”

Section: Methodsmentioning

confidence: 99%

Baseline characteristics, chromosomal alterations, and treatment affecting prognosis of deletion 17p in newly diagnosed myeloma

et al. 2016

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Deletion 17p13, del(17p), is associated with poor outcome in myeloma but some patients show long-term survival. With the current study we intended to identify factors impacting outcome of such high risk patients. We analyzed 110 newly diagnosed, symptomatic patients with del(17p) detected by fluorescence in situ hybridization (FISH) in CD138-purified myeloma cells to identify prognostic factors for survival. Age >65 years, ISS III, and elevated LDH negatively impacted survival. Patients with subclonal (10-60% of plasma cells) del(17p) had longer progression-free survival (PFS) than patients with del(17p) in >60% of plasma cells (26 vs. 19 months, P = 0.03). Additional gain of 1q21 was associated with shorter PFS (17 vs. 25 months, P = 0.01). Hyperdiploidy did not ameliorate impact of del(17p), but gain 19q13 predicted longer PFS (30 vs. 18 months, P = 0.01) and overall survival (50 vs. 29 months, P = 0.01). Multivariate analysis in transplant eligible patients (≤65 years) revealed better survival for patients treated with upfront autologous transplantation (hazard ratio, [95% confidence interval]: 0.15 [0.04, 0.58], P = 0.006). Application of maintenance therapy was associated with better survival in transplant-eligible patients (0.30 [0.09, 0.99], P = 0.05). We demonstrate heterogeneous outcome of patients with del(17p) according to baseline characteristics and treatment. 19q13 should be included in routine FISH panel, since gains were associated with better survival. Am. J. Hematol. 91:E473-E477, 2016. © 2016 Wiley Periodicals, Inc.

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“…However, biomodulatory therapies are increasingly available, including master modifiers, affecting particularly progression-free survival 2 (PFS2). That means that pro-anakoinotic therapies administered as pre-treatments, influence the outcome of subsequent therapies, contrasting tumor progression (58,142,161,162). Pro-anakoinotic therapies lead to long-lasting responses through long-lasting changes in tumor tissue and by modifications of the tumors' communications-mediated system state (Figures 2, 3).…”

Section: Perspectives Anakoinosis: Diversifying Non-curative Carementioning

confidence: 99%

Anakoinosis: Correcting Aberrant Homeostasis of Cancer Tissue—Going Beyond Apoptosis Induction

et al. 2019

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The current approach to systemic therapy for metastatic cancer is aimed predominantly at inducing apoptosis of cancer cells by blocking tumor-promoting signaling pathways or by eradicating cell compartments within the tumor. In contrast, a systems view of therapy primarily considers the communication protocols that exist at multiple levels within the tumor complex, and the role of key regulators of such systems. Such regulators may have far-reaching influence on tumor response to therapy and therefore patient survival. This implies that neoplasia may be considered as a cell non-autonomous disease. The multi-scale activity ranges from intra-tumor cell compartments, to the tumor, to the tumor-harboring organ to the organism. In contrast to molecularly targeted therapies, a systems approach that identifies the complex communications networks driving tumor growth offers the prospect of disrupting or "normalizing" such aberrant communicative behaviors and therefore attenuating tumor growth. Communicative reprogramming, a treatment strategy referred to as anakoinosis, requires novel therapeutic instruments, so-called master modifiers to deliver concerted tumor growth-attenuating action. The diversity of biological outcomes following pro-anakoinotic tumor therapy, such as differentiation, trans-differentiation, control of tumor-associated inflammation, etc. demonstrates that long-term tumor control may occur in multiple forms, inducing even continuous complete remission. Accordingly, pro-anakoinotic therapies dramatically extend the repertoire for achieving tumor control and may activate apoptosis pathways for controlling resistant metastatic tumor disease and hematologic neoplasia.

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Impact of maintenance therapy on subsequent treatment in patients with newly diagnosed multiple myeloma: use of "progression-free survival 2" as a clinical trial end-point

Abstract: LETTERS TO THE EDITOR © F e r r a t a S t o r t i F o u n d a t i o n

Cited by 22 publications

References 12 publications

Progression with clinical features is associated with worse subsequent survival in multiple myeloma

Progression with clinical features is associated with worse subsequent survival in multiple myeloma

Baseline characteristics, chromosomal alterations, and treatment affecting prognosis of deletion 17p in newly diagnosed myeloma

Anakoinosis: Correcting Aberrant Homeostasis of Cancer Tissue—Going Beyond Apoptosis Induction

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