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Fixed-duration lenalidomide maintenance: considering
environmental value in multiple myeloma
by Max Piffoux and Sebastien Taillemite
Received: August 11, 2026.
Accepted: August 25, 2026.
Citation: Max Piffoux and Sebastien Taillemite. Fixed-duration lenalidomide maintenance: considering
environmental value in multiple myeloma.
Haematologica. 2026 Sept 3. doi: 10.3324/haematol.2026.301809 [Epub ahead of print]
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Fixed-duration lenalidomide maintenance: considering environmental value in multiple
myeloma
Max Piffoux1,2*, Sebastien Taillemite3
1 Centre Léon Bérard, Department of Medical Oncology, Lyon, France.
2 Hospices Civils de Lyon, Department of Medical Oncology, Lyon, France.
3 Ecovamed, Paris, France
*corresponding author: max.piffoux@lyon.unicancer.fr
Author contributions
MP and ST performed the calculations. MP wrote the first draft of the manuscript. MP and ST
reviewed and edited the manuscript and approved the final version.
Disclosure information
ST is the founder and director of Ecovamed, a consulting company specializing in carbon-
footprint assessment for the pharmaceutical industry. MP has no conflicts of interest to
disclose.
Comment
Kumar et al. recently reported the results of the ENDURANCE maintenance randomization,
comparing indefinite lenalidomide with a fixed 2 -year duration in patients with standard-risk
newly diagnosed multiple myeloma who were not undergoing upfront autologous stem -cell
transplantation.1 Continuous maintenance improved progression -free survival but did not
improve overall survival, while grade ≥3 nonhematologic adverse events were more frequent.1
These findings contribute to the ongoing discussion regarding the optimal duration of
maintenance therapy. We suggest that they also illustrate a broader and largely unmeasured
consequence of treatment de-escalation: its potential environmental co-benefits.
The environmental burden of health care is increasingly recognized as a contributor to
pollution-related health damage, and pharmaceuticals represent an important component of
this footprint. 2,3 Treatment duration is therefore not environmental ly neutral. This may be
particularly relevant in hematology, where maintenance strategies can expose large numbers
of patients to anticancer medicines for several years. De-escalation trials consequently provide
an opportunity to identify strategies that preserve patient outcomes while reducing treatment
burden and resource consumption.
To illustrate the potential magnitude of this effect in ENDURANCE, we reconstructed
incremental lenalidomide exposure from the published supplementary treatment -exposure
data.1 For each 3 -cycle interval beyond cycle 24 in the indefinite -maintenance arm, the
number of patients remaining on treatment was multiplied by the number of cycles and by the
dose-specific cradle -to-pharmacy-gate carbon footprint of a 21 -capsule lenali domide box.
Dose-specific footprints were derived from a hybrid life-cycle assessment approach previously
developed for oral medicines. 4 On this basis, fixed -duration maintenance would avoid
approximately 526 kg (95% uncertainty interval 190-1,347) carbon dioxide equivalents (CO₂e)
per patient compared with indefinite treatment. At the population-level, an illustrative U.S.
scenario of approximately 8,000 potentially relevant patients annually, corresponding to
roughly 4,200 metric tons CO ₂e avoided each year. Applying ReCiPe 2016 egalitarian health -
damage factors, these avoided emissions would correspond to approximately 53 disability -
adjusted life-years of future health damage avoided annually. 2 These estimates are intended
to contextualize the potential environmental magnitude of treatment duration rather than to
modify the clinical interpretation of ENDURANCE.
We deliberately restricted this illustration to lenalidomide exposure. Drug exposure could be
reconstructed directly from publish ed trial data and combined with product -level life-cycle
estimates. By contrast, reliably estimating the environmental consequences of adverse events,
dose modifications, toxicity monitoring, hospital care, or management of second primary
cancers would require patient-level resource-use data that were not reported. Incorporating
these components using generic assumptions would introduce substantial model dependence
and imply a degree of precision unsupported by the available data. Their exclusion therefore
provides a deliberately narrow estimate of the directly quantifiable drug -related effect while
potentially omitting additional environmental differences between the strategies. Subsequent
anticancer therapy could partially offset these savings, although no nprotocol treatment was
only modestly more frequent after fixed-duration maintenance.1
Environmental considerations should not determine treatment duration when clinically
meaningful benefits are at stake. In ENDURANCE, the progression -free-survival bene fit of
continued maintenance must be considered together with the absence of an overall -survival
benefit, treatment toxicity, second primary cancers, treatment burden, quality of life, and
patient preferences. 1 Environmental impact should enter this disc ussion as an additional
dimension of treatment value, rather than as a substitute for established clinical outcomes.
The implications extend beyond lenalidomide and beyond greenhouse -gas emissions. De -
escalation may reduce pharmaceutical production, packag ing and transportation, but also
monitoring, patient travel, waste generation, supportive care, and other health-care resource
use. These changes may affect climate change as well as resource depletion, ecotoxicity, air
pollution, and other environmental endpoints. Yet these consequences remain largely invisible
in conventional clinical trials. Recent work in oncology has highlighted several clinically
validated strategies , including shorter treatment duration, dose reduction, reduced visit
frequency, biomarker-guided treatment selection, and treatment omission, that may generate
environmental co-benefits even though these outcomes were not prospectively assessed.5
Future maintenance and de -escalation trials could address this gap with relatively modest
additional data collection. Treatment exposure, dose modifications, hospitalizations,
outpatient visits, laboratory and imaging procedures, patient travel, and major supportive-care
interventions are frequently already collected or could be captured prospecti vely. Combined
with transparent life-cycle inventories and standardized environmental impact factors, these
data could allow environmental outcomes to be evaluated alongside survival, toxicity, quality
of life, and cost. Carbon footprint provides an intui tive starting point, but sustainability
assessment should ultimately evolve toward a broader life -cycle perspective rather than
equating environmental impact with greenhouse-gas emissions alone.
The ENDURANCE results therefore raise a question extending beyond the optimal duration of
lenalidomide maintenance: when therapeutic strategies achieve similar survival, should we
systematically assess which achieves that outcome with less treatment burden and lower
environmental impact? Doing so would not lower the evidentiary standard for hematologic
care. It would broaden our understanding of treatment value and help identify strategies that
are simultaneously clinically sound, patient -centered, economically responsible, and
environmentally sustainable.
References
1. Kumar S, Jacobus S, Cohen AD, et al. Continuous or fixed-duration maintenance therapy in multiple
myeloma. N Engl J Med. 2026;395(3):221-232.
2. Ducrot C, Péron J, Delaye M, Pérol D, Durand-Zaleski I, Piffoux M. Integrating environmental impact
in health technology assessment: an exploratory study. Pharmacoeconomics. 2025;43(10):1205-1222.
3. Lenzen M, Malik A, Li M, et al. The environmental footprint of health care: a global asse ssment.
Lancet Planet Health. 2020;4(7):e271-e279.
4. Piffoux M, Le Tellier A, Taillemite Z, Ducrot C, Taillemite S. Carbon footprint of oral medicines using
hybrid life cycle assessment. J Clean Prod. 2024;475:143576.
5. Delaye M, Matte P , Turpin A, et al. Improving cancer care while reducing its carbon footprint: GHG-
mitigating strategies highlighted at ESMO 2025. BJC Rep. 2026;4(1):30.