Lenalidomide-based combined therapy induced alterations in serum proteins of multiple myeloma patient: a follow-up case report and overview of the literature
Aim : Multiple myeloma (MM) is a malignant neoplasm of plasma cells (PC) derived from the bone marrow (BM) origin. The present case report was aimed to monitor the efficiency of lenalidomide-based combined therapy (LBCT) induced alterations in serum proteins of 42-year-old female MM patient. Besides...
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| Cite this: | Lenalidomide-based combined therapy induced alterations in serum proteins of multiple myeloma patient: a follow-up case report and overview of the literature / C.S. Senthilkumar, N. Ganesh // Experimental Oncology. — 2012. — Т. 34, № 4. — С. 373-376. — Бібліогр.: 23 назв. — англ. |
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nasplib_isofts_kiev_ua-123456789-1398672025-02-09T14:14:36Z Lenalidomide-based combined therapy induced alterations in serum proteins of multiple myeloma patient: a follow-up case report and overview of the literature Senthilkumar, C.S. Ganesh, N. Short communications Aim : Multiple myeloma (MM) is a malignant neoplasm of plasma cells (PC) derived from the bone marrow (BM) origin. The present case report was aimed to monitor the efficiency of lenalidomide-based combined therapy (LBCT) induced alterations in serum proteins of 42-year-old female MM patient. Besides, in the context of case report we also present an overview of the literature describing LBCT. Study design: Serum protein electrophoresis (SPEP) was performed in three visits (V1-V3) to monitor the disease status of the patient and her treatment response to LBCT. Level of monoclonal protein (M-protein) was measured through cellulose acetate zone electrophoresis and quantified by densitometer in follow-up investigations after therapy intervals. Results: A significant reduction of M-protein in γ-globulin region was observed (P < 0.007) after receiving LBCT. However, the condition depicted hyper γ-globulinemia. β-globulin (P < 0.002) and α2-globulin(P < 0.047) was suppressed from the initial visit and subsequent follow-up also indicated the status of hypoglobulinaemia. Although, serum albumin level was found to be increased after therapy (P < 0.016), hypoalbuminaemia was also noticed before and after LBCT. Conclusion: On the basis of this case report and pertinent literature, we conclude that LBCT is more efficient in the treatment of MM and has significant role in serum protein alterations especially in the reduction of M-protein in the MM patients. The authors thank the management of JNCHRC especially Chairman Mr. Madan Mohan Joshi, Institute Director Dr. K.V. Pandya, Medical Director and Radiation oncologist R. K. Pandey, Addt. Director Mr. Rakesh Joshi, Research coordinator Mrs. Divya Parashar for research support. 2012 Article Lenalidomide-based combined therapy induced alterations in serum proteins of multiple myeloma patient: a follow-up case report and overview of the literature / C.S. Senthilkumar, N. Ganesh // Experimental Oncology. — 2012. — Т. 34, № 4. — С. 373-376. — Бібліогр.: 23 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/139867 en Experimental Oncology application/pdf Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Short communications Short communications Senthilkumar, C.S. Ganesh, N. Lenalidomide-based combined therapy induced alterations in serum proteins of multiple myeloma patient: a follow-up case report and overview of the literature Experimental Oncology |
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Aim : Multiple myeloma (MM) is a malignant neoplasm of plasma cells (PC) derived from the bone marrow (BM) origin. The present case report was aimed to monitor the efficiency of lenalidomide-based combined therapy (LBCT) induced alterations in serum proteins of 42-year-old female MM patient. Besides, in the context of case report we also present an overview of the literature describing LBCT. Study design: Serum protein electrophoresis (SPEP) was performed in three visits (V1-V3) to monitor the disease status of the patient and her treatment response to LBCT. Level of monoclonal protein (M-protein) was measured through cellulose acetate zone electrophoresis and quantified by densitometer in follow-up investigations after therapy intervals. Results: A significant reduction of M-protein in γ-globulin region was observed (P < 0.007) after receiving LBCT. However, the condition depicted hyper γ-globulinemia. β-globulin (P < 0.002) and α2-globulin(P < 0.047) was suppressed from the initial visit and subsequent follow-up also indicated the status of hypoglobulinaemia. Although, serum albumin level was found to be increased after therapy (P < 0.016), hypoalbuminaemia was also noticed before and after LBCT. Conclusion: On the basis of this case report and pertinent literature, we conclude that LBCT is more efficient in the treatment of MM and has significant role in serum protein alterations especially in the reduction of M-protein in the MM patients. |
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Senthilkumar, C.S. Ganesh, N. |
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Senthilkumar, C.S. Ganesh, N. |
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Senthilkumar, C.S. |
| title |
Lenalidomide-based combined therapy induced alterations in serum proteins of multiple myeloma patient: a follow-up case report and overview of the literature |
| title_short |
Lenalidomide-based combined therapy induced alterations in serum proteins of multiple myeloma patient: a follow-up case report and overview of the literature |
| title_full |
Lenalidomide-based combined therapy induced alterations in serum proteins of multiple myeloma patient: a follow-up case report and overview of the literature |
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Lenalidomide-based combined therapy induced alterations in serum proteins of multiple myeloma patient: a follow-up case report and overview of the literature |
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Lenalidomide-based combined therapy induced alterations in serum proteins of multiple myeloma patient: a follow-up case report and overview of the literature |
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lenalidomide-based combined therapy induced alterations in serum proteins of multiple myeloma patient: a follow-up case report and overview of the literature |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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2012 |
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Short communications |
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Lenalidomide-based combined therapy induced alterations in serum proteins of multiple myeloma patient: a follow-up case report and overview of the literature / C.S. Senthilkumar, N. Ganesh // Experimental Oncology. — 2012. — Т. 34, № 4. — С. 373-376. — Бібліогр.: 23 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
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2025-11-26T17:45:25Z |
| last_indexed |
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1849875899032272896 |
| fulltext |
Experimental Oncology ��� �������� ���� ��ecem�er���� �������� ���� ��ecem�er� ��ecem�er� ���
LENALIDOMIDE-BASED COMBINED THERAPY INDUCED
ALTERATIONS IN SERUM PROTEINS OF MULTIPLE MYELOMA
PATIENT: A FOLLOW-UP CASE REPORT AND OVERVIEW
OF THE LITERATURE
C.S. Senthilkumar*, N. Ganesh
Clinical Cytogenetic Laboratory, Department of Research,
Jawaharlal Nehru Cancer Hospital & Research Centre (JNCHRC), Bhopal — 462 001 Madhya Pradesh, India
Aim: Multiple myeloma (MM) is a malignant neoplasm of plasma cells (PC) derived from the bone marrow (BM) origin. The
present case report was aimed to monitor the efficiency of lenalidomide-based combined therapy (LBCT) induced alterations
in serum proteins of 42-year-old female MM patient. Besides, in the context of case report we also present an overview of the
literature describing LBCT. Study design: Serum protein electrophoresis (SPEP) was performed in three visits (V1-V3) to monitor
the disease status of the patient and her treatment response to LBCT. Level of monoclonal protein (M-protein) was measured
through cellulose acetate zone electrophoresis and quantified by densitometer in follow-up investigations after therapy intervals.
Results: A significant reduction of M-protein in γ-globulin region was observed (P < 0.007) after receiving LBCT. However, the
condition depicted hyper γ-globulinemia. β-globulin (P < 0.002) and α2-globulin (P < 0.047) was suppressed from the initial visit
and subsequent follow-up also indicated the status of hypoglobulinaemia. Although, serum albumin level was found to be increased
after therapy (P < 0.016), hypoalbuminaemia was also noticed before and after LBCT. Conclusion: On the basis of this case report
and pertinent literature, we conclude that LBCT is more efficient in the treatment of MM and has significant role in serum protein
alterations especially in the reduction of M-protein in the MM patients.
Key Words: disease response monitoring; lenalidomide-based combined therapy; multiple myeloma; three visits follow-up; serum
protein alterations.
Multiple myeloma �MM� is a malignancy of plasma
cells �PC� of �one marrow �BM� [�]. MM �egins with
the elevated num�er of PC secretes whole monoclonal
immunoglo�ulin’s �Ig� or high level of homogenous
M-proteins [�]. M-protein secreting PC grows pri-
marily in the BM cavities and proliferates from one
cavity to another. MM may progress as asymptomatic
or symptomatic forms and their complications include
unexplained �one pain� typical elevated serum protein
or urinary protein� hypercalcemia� renal impairment�
amyloidosis� immunodeficiency and anemia [�� �].
Hematological� �iochemical� radiological and im-
munological investigations have gained more atten-
tion in esta�lishing the diagnosis and management
of MM. SPEP is the one considered as a hallmark im-
munological investigation in the diagnosis of MM over
years. SPEP identifies clinically significant M-protein
spike or paraprotein. M-protein is a tumor marker for
monoclonal gammopathies used to monitor the dis-
ease status. Monoclonal gammopathy is defined with
a homogeneous spike-like peak in a focal region of the
γ — glo�ulin [5]. Based on the diagnosis including
SPEP� MM patient must �e su�jected to chemotherapy
in a plateau state or for one year [�]. Many novel drugs
like �ortezomi�� thalidomide and lenalidomide has
made �etter understanding of MM treatment su�stan-
tially over the last decade [�].
Lenalidomide� an amino-su�stituted thalidomide
derivative is the current choice of drug to treat MM� due
to its high �eneficial �iological and pharmacological
properties in management of the disease. It is a well-
known oral immunomodulatory drug �IMi�� that
lacks the toxicological profile of thalidomide includes
significant peripheral neuropathy� somnolence� and
constipation [8� 9]. It has a remarka�le in vitro and
in vivo activity. Lenalidomide directly induces tumor
cell apoptosis [��]. Lenalidomide has the potential
to modify ligand induced cellular responses like tumor
necrosis factor-α �TNF-α� and interleukin-�β �IL-�β�.
It also stimulates the anti-inflammatory cytokine inter-
leukin-�� �IL-��� [��� ��]. Lenalidomide has a limited
toxicity in MM and myelodysplastic patients [��].
International uniform response criteria for MM also
recommended that patients undergoing therapy
and their measura�le disease must �e tracked and
assessed with SPEP [��]. Keeping in view of the
recommendations� the case presented here was
monitored for the therapeutic alterations induced
�y lenalidomide-�ased com�ined drugs �LBC��
through SPEP. Besides� in the context of case report
we also present an overview of the literature descri�-
ing similar therapy.
CASE REPORT
A ��-year-old Indian female who initially presented
with lower �ack ache. She is a known hypertensive with
Received: September 23, 2012.
*Correspondence: E-mail: sengenetics@gmail.com
Abbreviations used: BM — bone marrow; CR — complete remis-
sion; HM — hematological malignancies; Ig — immunoglobulin;
IL — interleukin; IMiD — immunomodulatory drug; LBCD — lenalid-
omide-based combined drugs; LBCT — lenalidomide-based com-
bined therapy; MM — multiple myeloma; M-Protein — monoclonal
protein; OD — once a day; PC — plasma cells; SPEP — serum pro-
tein electrophoresis; TLC — Total Leucocyte Count; TNF — tumor
necrosis factor; V — visit.
Exp Oncol ����
��� �� �������
��� Experimental Oncology ��� �������� ���� ��ecem�er�
to�acco chewing ha�it. Her past medical history was
remarka�le with hysterectomy a�out seven years ago.
She was examined �y primary care physician reported
pedal oedema and tenderness in lum�ar spine. She was
sent for MRI lum�osacral spine. MRI report revealed
generalized osteoporotic changes in spine� indicated
the possi�ility of multiple focal BM neoplastic lesions.
Finally� she was su�jected to whole �ody scan with
Tc-99m revealed multiple �ony metastases. She also
had complete �lood profile and �iochemistry test done
and the most nota�le finding showed Total Leucocyte
Count �TLC� ��.��� with an Hg� of 9.8 g/dL and �lood
urea �9%. Rest all other investigations were normal.
Additional studies recommended �y the oncologist
included SPEP.
Clinical Sample and SPEP. The study was con-
ducted in accordance to the ethical norms of Insti-
tutional human ethical committee. Peripheral �lood
sample were collected in no additive anticoagulant-free
vacutainer tu�es �VAKU-8� HM� Healthcare� UK� from
the patient through department of patho logy� Jawaha-
rlal Nehru Cancer Hospital & Research Centre� Bhopal.
Zone electrophoresis was performed immediately
within two hours after serum separation. Sera were
electrophoresed on cellulose acetate paper �Sarto-
rius� Germany� Electrophoresis unit �Bangalore Genei�
Bangalore� at �� V with Tris — Borate — E�TA �pH 8.��
�uffer conditions previously descri�ed �y us [�5� ��].
The �ands were separated till the dye front reaches
the end of cellulose acetate paper and then stained
with Ponceau S stain �S.d fine chemicals� Mum�ai�
and destained with �% acetic acid for �� min. Serum
protein �ands for each fraction were quantified for their
a�solute values in densitometer �Systronics� India�.
Diagnosis and chemotherapy regimen. Initial
SPEP analysis of the patient on visit � �V�� revealed
a discrete high intense �and confirmed the presence
of M-protein or strikingly elevated spike in the γ–
glo�ulin region. Accordingly to the diagnosis� she was
su�jected to radiotherapy and chemotherapy with the
com�ined regimen of lenalidomide ��5 mg� once a day
�O��� �examethasone ��� mg/week� and I�andronic
acid �Bisphosphonate� �9 mg/week�. Enoxaparin
��.� ml/O��� Morphine �� mg/O��� and Metoclo-
pramide �5 mg/O�� were administered as supportive
drugs in the regimen. She completed the first cycle
LBCT in two weeks. �ue to the complaint of continuous
vomiting� weakness and pain she was advised to stop
lenalidomide. After nine days� she started once again
LBCT as second cycle included anti�iotics Amikacin
��5� mg/O�� and Nitrofurantoin ���� mg/� days� due
to �acterial infections. To monitor the disease and its
response to LBCT in the patient� we collected serum
samples of visit � �V�� after two weeks of initial therapy
�at the end of first cycle� and visit � �V�� after two weeks
completion of the second cycle of lenalidomide. In all
the visits� SPEP was performed and analyzed as men-
tioned a�ove.
Statistical analysis. Statistical analysis was done
using Graph Pad InStat �GPIS� Ver. �.�5. One Sample
T test were used to analyze the cumulative results in 95%
confidence interval� at p < �.�5 significance level.
RESULTS
�isease status and response to LBCT was monitored
through SPEP in a female MM patient. Comparative
analysis was made among the individual protein frac-
tions �al�umin� α�-glo�ulin� α�-glo�ulin� β-glo�ulin and
γ-glo�ulin� among initial and follow — up visits �V��V��.
More significantly� a remarka�le reduction of M-pro-
tein spike or sharp intense �and in the γ-glo�ulin
region was o�served in V� and V� when compared
to V� �59.85±�.9�� �p < �.����. Although� the level
of M-protein was declined� percentage of γ-glo�ulin was
higher and a�ove the normal range even after therapy.
Since from V��V�� β-glo�ulin ��.9�� ± �.��� �p < �.����
and α�-glo�ulin �5.��� ± �.�8� �p < �.����� was markedly
suppressed and noticed as sharp faint �and conside-
ra�ly declined from the normal range. In all three visits�
α�-glo�ulin was seen as a faint �and and appeared within
the reference range �8.��� ± �.��� �p < �.����.
Al�umin appeared as a light diffused �and and
slightly increased after the therapy of V� and V� as com-
pared to V� ���.�� ± �.�5� �p < �.����. However� the low
serum al�umin level failed to attain the normal range
in V� and V� �Ta�le� Figure�.
Table. Serum protein profile of MM patient in three consequent visits
Serum proteins
(refe rence range, %) V1 (BT) V2 (AT) V3 (AT) Mean ± SE One sample
t-test
Albumin (42–60) 16.33 23.79 25.21 21.77±2.75 t = 7.907
p < 0.015*
α1-globulin (2–11) 3.92 10.91 9.36 8.06±2.12 t= 3.804
p < 0.063
α2-globulin (9–21) 7.79 3.38 5.98 5.72±1.28 t = 4.467
p < 0.047*
β-globulin (4.5–15) 3.16 2.72 2.84 2.91±0.13 t = 22.135
p < 0.002*
γ-globulin (9–25) 68.78 59.17 51.61 59.85±4.97 t = 12.047
p < 0.007*
Notes: BT — before therapy; AT — after therapy; * — significance.
Elevated Decreased
γ-Globulin
β-Globulin
α2-Globulin
α1-Globulin
Albumin
γ-Globulin
β-Globulin
α2-Globulin
α1-Globulin
Albumin
γ-Globulin
β-Globulin
α2-Globulin
α1-Globulin
Albumin
V1 V2 V3
Figure. Protein profile in serum of MM patient showing the
discrete intense �and of “Myeloma Protein” decreased after
receiving LBCT — Elevated — �ecreased
DISCUSSION
MM is an uncommon cancer occurs approximately
�����% of all hematological malignancies �HM�
[��]. Several anticancer chemotherapeutic drugs are
known to alter the immune cell functions and also
used as an immunosuppressant [�8]. Lenalidomide
is an IMi�� frequently used to treat MM� HM and solid
tumors. Hence� the case presented here was monitored
for the therapeutic effects of LBC� on serum proteins.
Many studies suggested that the LBCTs are highly
effective to treat MM. Even though lenalidomide has
Experimental Oncology ��� �������� ���� ��ecem�er���� �������� ���� ��ecem�er� ��ecem�er� ��5
an antitumor activity� some MM patients do not respond
to monotherapy [�9]. Lenalidomide monotherapy
in MM may possi�ly delay in complete remission �CR�
of the disease and drug must �e administered for a long
period to achieve sta�le remission. Such long adminis-
tration may cause side effects. A phase II study revealed
�5% of relapsed or refractory MM patients treated with
lenalidomide showed a complete and partial response.
However� these patients failed to respond lenalidomide
monotherapy� �9% of the patients responded after the
addition of oral dexamethasone [��]. Another study
o�served lenalidomide plus dexamethasone com�ined
therapy as a highly effective regimen to treat refractory
MM as compared to the old therapy consisting of high-
dose dexamethasone alone [��].
An open-la�el phase II trial� studied �� symptom-
atic MM naive patients received oral lenalidomide
��5 mg/O�� for �� days� clarithromycin �5�� mg� twice
daily� and dexamethasone ��� mg� once weekly every
�8 days. This study significantly o�served a reduction
of serum M-protein ≥ 5�% and urine M-protein ≥ 9�%
was noticed in 9�% of patients �n = �5�. Maximum
complete response rate was �9%� with ��% of patients
showed a decrease in M-protein levels around 9�%
[��]. The response rate of other LBC� regimen ��exa-
methasone� �ortezomi� and cyclophosphamide�
is also more encouraging in the treatment of relapsed
or refractory MM achieved CR [9].
Our patient has shown a remarka�le response after
receiving the LBCT demonstrated the sta�le reduction
of M-protein. Considera�le decrease of M-protein level
indicated patient’s response to com�ined therapy. How-
ever� hyper γ-glo�ulinemia was retained in the patient
even after the therapy. Furthermore� the com�ined
regimen is highly effective than any other monotherapy
and administered regularly to achieve CR in the patient.
Regular administration of lenalidomide may have re-
duced side effects in the MM patient [��].
Besides� other glo�ulin proteins �β and α�� persisted
in a suppressive state indicated the condition of hypo-
glo�ulinaemia �efore and after therapy. Remarka�ly�
the status of α�-glo�ulin was normal in the patient even
after receiving two cycles of lenalidomide. Low serum
al�umin level or hypoal�uminaemia commonly occurs
in myelo�lastic or lympho�lastic leukemic events [��].
In agreement to this hypothesis� hypoal�uminaemia
was also existed in the patient �efore and after therapy�
a slight increase in al�umin status indicated the posi-
tive response only after the initial therapy. However� the
case report presented here illustrated the condition
of monoclonal gammopathy in all three visits.
The present case findings are concordance to the
report of We�er et al. [��] and Niesvizky et al. [��]�
suggested that CR in MM patients can �e achieved
on LBCT. However� the present study failed to monitor
the MM patient till CR� due to her irregular follow-up and
discharge. But� this three visit follow-up noticed a �etter
response of the MM patient on LBCT. It is also notewor-
thy to mention that LBCT has a significant role in the
reduction of M-protein. This reduction may �e due to the
immunomodulating activity of lenalidomide. On the
�asis of case report we suggest that LBCT regimen
is effective against MM and must �e implemented for
treating other cancers similar to MM.
Although this follow-up report has few limitations�
the case reported here exhi�its the advantage and
efficiency of LBCT� which could �e useful to the la�ora-
tory clinicians and oncologists in treating MM. Effective
treatment of cancer needs a proper chemotherapeutic
regimen and monitoring attains CR in the patients.
Hence� this kind of case report is essential in future
to reveal the therapeutic effect of drugs in cancer
treatment.
In summary� this case report highlights the signifi-
cance of monitoring serum protein alterations espe-
cially M-protein through SPEP. We conclude that LBCT
has a potent role in treating MM.
ACKNOWLEDGEMENT
The authors thank the management of JNCHRC
especially Chairman Mr. Madan Mohan Joshi� Institute
�irector �r. K.V. Pandya� Medical �irector and Radia-
tion oncologist R. K. Pandey� Addt. �irector Mr. Rakesh
Joshi� Research coordinator Mrs. �ivya Parashar for
research support.
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