Page 172 - Haematologica Vol. 107 - September 2022

ARTICLE - Immune deficiency during RM after transplantation L. Bouard et al. Table 4. Multivariate analysis for infectious episode, neutropenia, hypogammaglobulinemia and CD4 lymphopenia.
Modality
OR
95% CI
P
Infectous episode
>9 ritux inj
11.17
2.482-50.263
0.0017
Neutropenia
-
-
-
-
Hypogammaglobulinemia <6x109/L
Classical morphologic variant Morphologic CR
>9 ritux inj
0.278 2.972 4.278
0.086-0.899
1.263-6.994 1.393-13.141
0.033 0.013 0.011
Hypogammaglobulinemia <4x109/L
>9 ritux inj
2.882
1.131-73.450
0.027
CD4 lymphopenia
PS 0 at diagnosis
0.423
0.220-0.812
0.010
Inj: injection; CR: complete response; PS: performance status; int: interval; OR: odds ratio; CI: confidence interval; ritux: rituxi- mab.
each center. Lack of efficacy of the Ig substitution might
suggest that other factors could also be involved or that
Ig substitution fails to restore an active humoral immun-
ity. Therefore, our study questions the relevance of Ig
substitution which has an added financial cost. In the
absence of a prospective randomized study, our study
does not call for a systematic use of Ig substitution, in-
cluding for patients with recurrent infections. Another
interesting finding of our work is the relationship between hypogammaglobulinemia and complete response, as well
as prolonged duration of response. Although there is a
guaranteed time bias as hypogammaglobulinemia can de-
velop only late post transplant, very few patients presented
an hypogammaglobulinemia after having recovered an Ig
level superior of 6 g/L and the relationship between hypo-
gammaglobulinemia and PFS was still significant when ad-
justed on the number of rituximab injections. Moreover, we
conducted a landmark methodology (every 2 months from
M2 to M36) which did not highlight the appropriate and
precise time point for monitoring Ig level. This might sug-
gest that rituximab-induced B-cell depletion indirectly re-
flect the rituximab anti-MCL effect. This hypothesis is
supported by the multivariate analysis showing a dose ef-
fect relationship between rituximab and hypogammaglob-
ulinemia. However, improved PFS forfundedbyRocheSAS. hypogammaglobulinemic patients does nor only reflect a
rituximab dose effect, as it is still significant when adjusted on number of rituximab injections. Other parameters such as FCGR3A gene polymorphism could also explain discrep-
References
1. Jain P, Wang M. Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management. Am J Hematol. 2019;94(6):710-725.
2. Dreyling M, Campo E, Hermine O, et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice
Data-sharing statement
Data of the present work will be shared upon request to the corresponding author.
Guidelines for diagnosis, treatment and follow-up. Ann Oncol.
2017;28(Suppl 4):S62-71.
3. Le Gouill S, Thieblemont C, Oberic L, et al. Rituximab after
autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017;377(13):1250-1260.
ancies between patients in terms of rituximab anti-MCL ef- fect.18,19
In conclusion, our work highlights the B-cell and humoral immunodepression induced by RM as from 1-year post transplant in MCL patients. Prior to 1 year, humoral immune status reflects effects of rituximab before the transplant and the transplant procedure itself. RM does neither induce a higher incidence of neutropenia nor T CD4 depletion which are the result of the transplant procedure. Ig sub- stitution remains an open question although it doesn’t ap- pear to balance the hypogammaglobulinemia-induced infections. Interestingly, hypogammaglobulinemia could become a surrogate marker for the RM anti-MCL effect.
Disclosures
No conflicts of interest to disclose.
Contributions
Funding
This work is an ancillary study of The LyMa trial which was
LB and SLG performed the research and wrote the manu- script; BT and SB analyzed the data. All other authors gave advice and supervised the writing of the manuscript.
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