_____________________________________________________________________________________________________ 
 
*Corresponding author: E-mail: meriche.h23@gmail.com; 
 
Cite as: Hacene Meriche, Sara Zaghez, Feriel Sandra Bouafia, Boutheina Abdaoui, Nacima Sabiha Gadiri, and Hichem Frigaa. 
2025. “Symptomatic Multiple Myeloma in the Second Trimester of Pregnancy: A Case Report”. Asian Journal of Immunology 8 
(1):222–229. https://doi.org/10.9734/aji/2025/v8i1173. 
 

 
 

Asian Journal of Immunology 
 
Volume 8, Issue 1, Page 222-229, 2025; Article no.AJI.141940 
 

 
 

 

 

Symptomatic Multiple Myeloma in the 
Second Trimester of Pregnancy: A 

Case Report 
 

Hacene Meriche a*, Sara Zaghez a, Feriel Sandra Bouafia a,  

Boutheina Abdaoui a, Nacima Sabiha Gadiri a  

and Hichem Frigaa b 
 

a Department of Immunology, Clinic Sainte Therese UHC, Annaba, Algeria. 
b Department of Nephrology, Hospital Ibn Sina, UHC, Annaba, Algeria. 

 
Authors’ contributions  

 
This work was carried out in collaboration among all authors. All authors read and approved the final 

manuscript. 
 

Article Information 
 

DOI: https://doi.org/10.9734/aji/2025/v8i1173  
 

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Received: 10/07/2025 
Published: 15/09/2025 

 
 
ABSTRACT 
 

Multiple myeloma (MM) in pregnant women is a rare disease characterized by clonal proliferation of 
plasma cells producing monoclonal immunoglobulin, which suppresses the normal production of 
other antibodies and weakens the maternal immune response. Plasma cells release inflammatory 
cytokines (IL-6, TNF-α, IL-1β) that promote their survival and bone destruction. During pregnancy, 
maternal immunity shifts towards complex tolerance with decreased Th1 inflammatory responses, 
Th2 predominance, and increased regulatory T cells, which often masks MM and complicates its 
management. Treatment is generally deferred until after delivery to protect the fetus, with the VTD 
protocol then used to control the disease by reducing plasma cell proliferation and inflammation. 

Case Report 

https://doi.org/10.9734/aji/2025/v8i1173
https://pr.sdiarticle5.com/review-history/141940


 
 
 
 

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223 

 

This case illustrates the importance of simple tests such as serum protein electrophoresis in 
diagnosing unexplained anemia during pregnancy, and highlights the need for immunological 
monitoring and a multidisciplinary approach to optimize maternal and fetal prognosis. 

 

 
Keywords: Multiple myeloma; pregnancy; anemia; monoclonal composant; electrophoresis. 
 

1. INTRODUCTION 
 
Multiple myeloma is a malignant clonal 
proliferation of plasma cells characterized by 
excessive monoclonal production of 
immunoglobulins, mainly IgG. The median age at 
diagnosis is generally around 63 to 70 years, 
with cases in young people, and particularly 
during pregnancy, remaining extremely rare, with 
fewer than 50 cases described in the global 
literature since 1965 (Durand, 2024; Hila et al. 
2022). Myeloma in pregnancy is a rare 
occurrence as the median age of myeloma 
diagnosis is around the sixth and seventh 
decade of life and is more commonly observed in 
males. The first case of myeloma in pregnancy 
was reported in 1965, and since then there have 
been fewer than fifty cases reported worldwide. 
Although only three percent of cases are 
diagnosed below the age of forty, myeloma is 
now increasingly being diagnosed in younger 
ages and during pregnancy due to better 
screening and awareness (Szydełko, 2019). 
Gestational anemia is common, but in the 
presence of a monoclonal peak, further 
investigation is necessary to rule out an 
underlying blood disorder and ensure appropriate 
management. However, diagnosis is complicated 
by the overlap with the physiological symptoms 
of pregnancy. Therefore, particular vigilance is 
required. 
 

2. CASE PRESENTATION 
 
A 35-year-old patient from Annaba (Algeria), 24 
weeks pregnant with her second child, with no 
notable family history. She complains of 
persistent fatigue accompanied by pale skin. 
Clinical examination revealed marked pallor, a 
uterine fundus consistent with 24 weeks, a 
normal fetal heart rate (140 bpm), and a high 
body mass index of 28 kg/m². Blood pressure 
was stable at 120/80 mmHg. 
 

2.1 Biological and Hematological Tests 
 
Blood count reveals moderate anemia (Hb 10 
g/dL, hematocrit 30%, MCV 75 fL), associated 

with low ferritin (22 ng/mL) indicative of probable 
iron deficiency. Blood smear shows anisocytosis, 
polychromatophilia, presence of erythroblasts, 
neutrophilic hyperleukocytosis with coarse 
granulations, and moderate thrombocytopenia. 
The sedimentation rate was accelerated (78 
mm/h). Serum protein electrophoresis  (Sebia) 
revealed a monoclonal IgG kappa peak of 42 g/L, 
confirmed by immunofixation. Serum free light 
chain assay  (Sebia) showed a high κ/λ ratio 
(3.86). Bence Jones proteinuria was positive. In 
addition, mild renal failure is observed with a 
slight increase in urea (9.8 mmol/L), creatinine 
(165 µmol/L), and proteinuria at 650 mg/24h. 
Moderate hypercalcemia (2.85 mmol/L) and a 
liver profile consistent with pregnancy-related 
cholestasis complete the picture (Figs. 1, 2, 3). 
 

2.2 Morphological and Radiological 
Examinations 

 
The bone marrow aspiration revealed significant 
plasma cell infiltration estimated at 65%, which 
was confirmed as clonal by immunophenotyping 
(CD38+, CD138+, CD56+) using flow cytometry 
(BD FACS Lyric). A low-dose whole-body CT 
scan detected a 6 mm osteolytic lesion in the 
pelvis, typical of bone involvement associated 
with multiple myeloma. Abdominal and obstetric 
ultrasounds showed a normal fetus with no 
abnormalities or growth retardation, and 
measurements were within normal limits. These 
examinations, which limit fetal exposure to 
radiation, are essential for assessing the extent 
of the disease while ensuring safe, risk-free 
maternal-fetal monitoring. 
 

2.3 Diagnosis 
 
The diagnosis of symptomatic multiple myeloma 
in the patient was based on the combination of a 
significant monoclonal IgG kappa peak 
associated with a high κ/λ ratio, with positive 
Bence Jones proteinuria indicating significant 
renal involvement, as well as high                          
myeloid plasma cell infiltration (65%) with 
characteristic immunophenotyping (CD38+, 
CD138+, CD56+).  



 
 
 
 

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224 

 

 
 

Fig. 1. The electrophoretic profile of our patient's serum proteins, performed on agarose gel, 
shows a monoclonal band located in the gamma globulin zone at position 21. This observation 

confirms the presence of a monoclonal immunoglobulin, attesting to the clonal nature of the 
detected protein 

 

 
 

Fig. 2. The electrophoretic pattern of the protein profile at position 21 shows a monoclonal 
peak in the gamma globulin zone, with an estimated concentration of 40 g/L, accompanied by 

a decrease (suppression) in other classes of polyclonal immunoglobulins 



 
 
 
 

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Clinically, the presence of anemia, renal failure, 
hypercalcemia, and osteolytic bone lesions 
meets the CRAB criteria of the IMWG 
(International Myeloma Working Group), 
justifying a diagnosis of myeloma in the active 
phase. The ISS  (International Staging System 
)classification of stage II reflects a high tumor 
burden and a guarded prognosis. This complex 
diagnosis requires appropriate management, 
which is even more delicate in the case of 
pregnancy. 
 

2.4 Management and Follow-Up 
 
Due to the high teratogenic risk, chemotherapy is 
postponed during pregnancy, especially during 
the first and second trimesters, with regular 

monthly clinical and biological monitoring based 
on blood counts, renal function tests, calcemia 
measurements, protein electrophoresis (Fig. 
4a/b), and weekly ultrasounds to ensure 
maternal-fetal stability and a complication-free 
pregnancy. After delivery, treatment with the VTD 
protocol (treatment using bortezomib (Velcade), 
lenalidomide (Revlimid), and dexamethasone), 
which is effective and well tolerated, leading to 
complete remission.  
 
This success highlights the importance of 
appropriate and deferred treatment, combined 
with multidisciplinary post-treatment follow-up 
(hematologist, gynecologist, nephrologist, 
immunologist) to detect any relapses or side 
effects and ensure optimal long-term care. 

 

 
 

Fig. 3. Immunofixation results from our case show that the monoclonal peak corresponds to 
an IgG kappa immunoglobulin, with a decrease in other types of polyclonal immunoglobulins 

 

 
4 a. 



 
 
 
 

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226 

 

 
4b. 

 
Fig. 4 a/b. Regression of the monoclonal peak after postpartum treatment with the VTD 

protocol in our patient with gestational myeloma 
 

3. DISCUSSION 
 
Multiple myeloma (MM) is a malignant blood 
disorder characterized by clonal proliferation of 
plasma cells in the bone marrow, associated with 
excessive monoclonal production of 
immunoglobulins (Kyle & Rajkumar, 2004). The 
IgG kappa form identified in our patient 
corresponds to the most frequently observed 
type in the general population, which is 
consistent with the epidemiological and biological 
data reported by Palumbo and Anderson (2011) 
and corroborated by Kyle and Rajkumar (2004) ; 
Palumbo & Anderson, 2011 ; Johns Hopkins 
University School of Medicine, 2024). 
Immunoparesis, resulting from the suppression 
of polyclonal immunoglobulins, is a mechanism 
well described in the literature, promoting 
significant immunosuppression and vulnerability 
to opportunistic infections (Rajkumar, 1999 ; La 
Revue du Praticien, 2023). This 
immunosuppression was highlighted by 
Rajkumar (2011), who emphasized its prognostic 
effect and therapeutic implications, in line with 
the clinical observations made in our patient. 
Epidemiologically, MM primarily affects older 
populations, with less than 3% of cases 
diagnosed before the age of 40, which is linked 
to female fertility (Steinbach, 2024 ; Abdellah et 

al., 2020). Our observation is thus consistent with 
the rare descriptions of MM in the context of 
pregnancy, as confirmed by the reviews by 
Kumar et al. (2003) and Lee et al. (2016), which 
emphasize the rarity and complexity of 
management in this specific situation (Szydełko, 
2019 ; Pajor, 1991). The clinical presentation of 
MM during pregnancy is often atypical. Anemia, 
which is very common during pregnancy, 
particularly due to nutritional deficiencies, is a 
common factor that can lead to delayed 
diagnosis of serious conditions such as MM. This 
is clearly illustrated in our observation by anemia 
that is refractory to iron treatment, a situation 
also highlighted by Smith et al. (2012), who 
recommend thorough investigation of persistent 
unexplained anemia in pregnant women (Mor & 
Cardenas, 2010). Serum protein electrophoresis 
and free light chain assay, as indicated in our 
diagnosis, are now considered key tests for the 
early detection of subtle monoclonal peaks and 
imbalances in the κ/λ ratio ratio imbalances 
(Terpos & Dimopoulos, 2005). These 
investigations are systematically recommended 
in the literature and their importance is 
unanimously recognized, particularly in the 
reviews by Gertz (2008) and Terpos & 
Dimopoulos (2005), confirming the relevance of 
our diagnostic approach (Faze, 2019 ; Borja, 



 
 
 
 

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227 

 

2011). Pregnancy alters the immune system, 
inducing maternal-fetal tolerance by reducing 
cellular and humoral immune responses 
(Palumbo et al., 2020). This modulation can 
attenuate the classic symptoms of MM (fatigue, 
recurrent infections, bone pain), explaining the 
late or incidental discovery of cases during 
pregnancy—a point that our observation 
corroborates in perfect agreement with the work 
of Mor & Cardenas (2010) and Lee et al. (2016) 
(Dispenzieri et al., 2019 ; Pajor, 1991). From an 
immunopathological perspective, IL-6 plays a 
major role in the proliferation of malignant 
plasma cells and in the development of bone 
lesions through the activation of osteoclasts 
(Rajkumar, 2020). As observed in our patient, 
this mechanism is responsible for the common 
disabling bone complications of MM, suggesting 
the need for increased vigilance, particularly in 
the context of pregnancy, where osteoarticular 
symptoms can be confused with physiological 
pain associated with pregnancy (Terpos & 
Dimopoulos, 2005). This issue is discussed at 
length by Terpos and Dimopoulos (2005) and 
Terpos et al. (2020) (Rajkumar, 2020 ; Elgabry et 
al., 2023). The therapeutic management of MM 
during pregnancy remains a major challenge. 
The literature, including the study by Lee et al. 
(2018), recommends a cautious approach, 
generally deferring active treatment until after 
delivery to avoid the teratogenic effects of 
conventional chemotherapy, particularly in the 
first trimester (Rajkumar, 2011). This strategy, 
with close multidisciplinary follow-up, 
corresponds exactly to the management protocol 
we applied, reflecting perfect alignment with 
current best practices (Rajkumar, 2020; Smith, 
2021). The standard postpartum treatment for 
symptomatic multiple myeloma is the combined 
VTD protocol (bortezomib, thalidomide, 
dexamethasone), recognized for its efficacy and 
good tolerance, validated by several studies, 
including that of Palumbo et al. (2020). New 
therapeutic options, such as monoclonal 
antibodies and newer proteasome inhibitors, are 
currently being evaluated, although data in 
pregnant women remain limited, as highlighted 
by Dispenzieri et al. (2019). The protocol used in 
this case is consistent with current 
recommendations and advances in the treatment 
of multiple myeloma. Finally, the importance of 
early diagnosis in cases of persistent                       
anemia in pregnant women, as highlighted in our 
case, is shared by many authors                              
(Terpos,2020a, 2020b). Increased awareness 
among clinicians to include specific 
immunological tests is necessary. 

4. CONCLUSION 
 

Symptomatic multiple myeloma during pregnancy 
represents an exceptionally rare and challenging 
clinical condition. Its diagnosis is often delayed 
because the presenting symptoms (fatigue, bone 
pain, anemia) are frequently misinterpreted as 
physiological changes of pregnancy.Moreover, 
the maternal immune alterations associated with 
feto-maternal tolerance further complicate both 
the clinical assessment and the interpretation of 
laboratory findings. 
 

Nevertheless, certain warning signs should 
prompt further investigation: a persistent, 
unexplained anemia refractory to iron 
supplementation, when associated with the 
detection of a monoclonal spike on serum protein 
electrophoresis, strongly suggests an underlying 
plasma cell dyscrasia. In such cases, a 
comprehensive immunological work-up (including 
immunofixation, quantitative immunoglobulins, 
and free light chain assay) is mandatory for the 
biological detection of multiple myeloma. 
 

From a therapeutic perspective, postponing 
chemotherapy until the postpartum period is 
generally recommended in order to minimize 
teratogenic risks to the fetus. During pregnancy, 
strict multidisciplinary monitoring involving 
hematologists, obstetricians, neonatologists, and 
anesthesiologists is required to maintain 
maternal and fetal stability. 
 

After delivery, treatment with the VTD protocol 
(Bortezomib, Thalidomide, Dexamethasone) has 
proven to be both effective and well tolerated, 
leading to complete remission and ensuring a 
favorable prognosis. 
 

Finally, the management of multiple myeloma 
during pregnancy requires a personalized and 
multidisciplinary approach, carefully balancing 
maternal safety, fetal protection, and the 
optimization of therapeutic outcomes in the 
postpartum period. 
 

CONSENT  
 

As per international standards or university 
standards, patient(s) written consent has been 
collected and preserved by the author(s). 
 

ETHICAL APPROVAL 
 

As per international standards or university 
standards written ethical approval has been 
collected and preserved by the author(s). 



 
 
 
 

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DISCLAIMER (ARTIFICIAL INTELLIGENCE) 
 
Author(s) hereby declare that generative AI 
technologies such as Large Language Models, 
etc. have been used during the writing or editing 
of manuscripts. This explanation will include the 
name, version, model, and source of the 
generative AI technology and as well as all               
input prompts provided to the generative AI 
technology 
 
Details of the AI usage are given below: 
 

1. Language and style enhancement 
2. Aide à la traduction 
3. Assistance in idea generation 

 

ACKNOWLEDGEMENTS 
 
We would like to thank the nephrology, 
immunology, and obstetrics and gynecology 
teams for their valuable collaboration. 
 

COMPETING INTERESTS 
 

Authors have declared that no competing 
interests exist. 
 

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