Program DHC-Virtual
20 - 21 January 2021
Clinical Abstracts session 3
Abstract
Revised frailty assessment in elderly myeloma patients
20 January
11:42 11:54
C. Stege
Paper

Improving the identification of frailty in elderly newly diagnosed multiple myeloma patients

Claudia Stege (1), Kazem Nasserinejad (2), Saskia Klein (3), Gert-Jan Timmers (4), Mels Hoogendoorn (5), Paula Ypma (6), Inger Nijhof (1), Gerjo Velders (7), Leonie Strobbe (8), Nazik Durdu-Rayman (9), Matthijs Westerman (10), Marjan Davidis-van Schoonhoven (11), Roel van Kampen (12), Aart Beeker (13), Ad Koster (14), Amanda Dijk (15), Niels van de Donk (1), Ellen van der Spek (16), Rineke Leys (17), Matthijs Silbermann (18), Kaz Groen (1), Nicole van der Burg-de Graauw (19), Harm Sinnige (20), Klaas van der Hem (21), Henriette Levenga (22), Yavuz Bilgin (23), Pieter Sonneveld (24), Mark-David Levin (25), Sonja Zweegman (1)
(1) Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Hematology, Amsterdam, (2) HOVON Data Center, Erasmus MC Cancer Institute, Hematology, Rotterdam, (3) Meander Medical Center, Internal Medicine, Amersfoort, (4) Amstelland Hospital, Internal Medicine, Amstelveen, (5) Medical Center Leeuwarden, Hematology, Leeuwarden, (6) Haga Hospital, Hematology, The Hague, (7) Ziekenhuis Gelderse Vallei, Internal Medicine, Ede, (8) Gelre Hospital, Internal Medicine, Zutphen, (9) Franciscus Hospital location Vlietland, Internal Medicine-Hematology, Schiedam, (10) Northwest Clinics, Internal Medicine, Alkmaar, (11) Beatrix Hospital, Internal Medicine, Gorinchem, (12) Zuyderland Medical Center, Internal Medicine-Hematology, Sittard-Geleen, (13) MBA Spaarne Gasthuis, Internal Medicine, Hoofddorp, (14) VieCuri Medical Center, Internal Medicine, Venlo, (15) St Jansdal Hospital, Internal Medicine, Harderwijk, (16) Rijnstate Hospital, Internal Medicine, Arnhem, (17) Maasstad ziekenhuis, Hematology and Oncology, Rotterdam, (18) Tergooi Hospital, Internal Medicine, Hilversum, (19) Bravis ziekenhuis, Internal Medicine, Roosendaal, (20) Jeroen Bosch Ziekenhuis, Internal Medicine, Den Bosch, (21) Zaans Medical Center, Internal Medicine, Zaandam, (22) Groene Hart Hospital, Internal Medicine, Gouda, (23) Admiraal de Ruijter Hospital, Internal Medicine, Goes, (24) Erasmus MC Cancer Institute, Hematology, Rotterdam, (25) Albert Schweitzer Hospital, Internal Medicine, Dordrecht
No potential conflicts of interest
Introduction

The level of frailty, as determined by the International Myeloma Working Group frailty index (IMWG-FI), clearly predicts the clinical outcome of elderly non-transplant eligible newly diagnosed multiple myeloma patients. However, with this index, age >80 years alone automatically classifies a patient as frail, which is at least questionable and possibly leads to under-treatment. Moreover, the IMWG-FI is not suitable yet to select the most vulnerable patients in whom treatment effect will be negligible or whom even will be done harm.  Therefore, we investigated the impact of the different frailty factors on treatment discontinuation, PFS and OS with the aim to improve the prognostic value of the IMWG-FI.         

Methods

The multicenter, non-randomized, phase 2, HOVON 123 trial (NTR4244) included patients aged 75 years or over with a newly diagnosed multiple myeloma. Patients were treated with 9 cycles dose-adjusted melphalan, prednisone and bortezomib. Geriatric assessments were performed at baseline. The primary endpoint was premature  treatment discontinuation (within 9 cycles). Frailty factors (age, CCI, ADL, iADL) predicting treatment discontinuation, PFS and OS were identified by Akaike’s Information Criterion (AIC) using a backward selection procedure in a logistic regression model.

Results

Two revised FIs (RFI) based on the IMWG-FI were developed, using a novel cut-off for frailty (≥3 versus ≥2; RFI-1) plus a modified assigned weight of comorbidities (CCI≥3 2 points versus 1 point; RFI-2), given their superior prognostic value for treatment discontinuation. These revised FIs identified a 45%-smaller frail population, without patients formerly defined frail based on an age >80 alone, who had more comorbidities and impairments in  (i)ADL, and an inferior survival as compared to the original IMWG-FI: median PFS 12.7 and 14.4 months versus 16.6 months; OS 23.7 and 26.4 months versus 35.0 months, with the RFI-1, RFI-2 and IMWG-FI, respectively. 

Conclusion

By reducing the importance of age >80 and increasing the weight of comorbidities, we identified a 45%-smaller but more vulnerable population of frail patients with an inferior clinical outcome, as compared to the original IMWG-FI. Our model can be used as a novel validation platform in differently treated patients in order to move from prognostic to predictive geriatric models.  

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