Author: admin

A previously health women in her 60s was diagnosed with high-risk mantle cell lymphoma. A year after enrolling in a clinical trial for a combination of monoclonal antibody, BTK inhibitor and BCL-2 inhibitor, she experienced complete remission with minimal side effects.

Case presentation

A retired middle school teacher sought medical attention for enlarged lymph nodes in her neck. This led to a biopsy, which led to a diagnosis of mantle cell lymphoma. Her spleen was also quite enlarged at 27 centimeters, which is roughly double the normal size. In addition, she had pancytopenia from bone marrow involvement with mantle cell lymphoma.

Her community oncologist recommended initiating bendamustine and rituximab. However, after reading that some mantle cell lymphoma doesn’t respond to chemotherapy, she reached out to Cleveland Clinic Cancer Institute for a second opinion.

With a team of seven lymphoma specialists, Cleveland Clinic Cancer Institute has a depth of experience treating patients with this somewhat rare condition, which represents less than 10% of non-Hodgkin’s lymphoma.

Further evaluation and testing showed that the patient’s tumor harbored a TP53 mutation, which is typically associated with poor outcomes.

“In recent years, the hematology community has increasingly recognized that patients with mantle cell lymphoma who have TP53 mutations in their biopsy specimens at the time of diagnosis are at increased risk of failure with chemotherapy,” explains Director of the Lymphoid Malignancies Program and Staff Physician Brian T. Hill, MD, PhD. “Patients with these mutations tend to respond better to BTK inhibitors and BCL-2 inhibitors.”

Treatment plan

The patient contacted the Institute’s Cancer Answer Line, whose goal is to arrange an appointment within seven days of the referral. “We really prioritize swift access to care because time is of the essence both in getting the disease under control and because patients are appropriately anxious,” says Dr. Hill. “Referring physicians also appreciate that if they need guidance with a challenging case, their patients can be seen quickly by one of our disease specialists.”

Based on the patient’s high-risk disease status and mutation status, Dr. Hill spoke with the patient and her husband about participating in a clinical trial where she would receive the monoclonal antibody rituximab in combination with the BTK inhibitor acalabrutinib and the BLC-2 inhibitor venetoclax. The goal was to provide her with treatment targeted for this mutation and spare her the side effects of traditional cytotoxic chemotherapy. The patient and her husband were eager to hear about alternatives to nonspecific chemotherapy, and she decided to participate in the trial.

“People often think of clinical trials as a last resort option and that’s not the case, especially in lymphoma,” says Dr. Hill. “We have so many good treatments and increasingly they’re being used in the frontline setting instead of chemotherapy. There are many clinical trial opportunities in the frontline setting as well as for patients who have relapsed. If your patient is at a fork in the road and you’re unsure of the right approach, I’d recommend speaking with a disease team specialist.”

After enrolling in the trial, the patient received IV rituximab monthly and the oral agents daily for roughly a year. All treatment was administered on an outpatient basis.

Outcome

The patient tolerated the treatment remarkably well. Aside from minor bruising on her arms, which is common with BTK inhibitors, she had few side effects. There were mild changes to her platelet count but there were no neutropenia, infections or other cytopenias.

PET scans were performed at baseline and at the end of treatment. The scans showed that the patient entered a complete metabolic response. Minimal residual disease (MRD) testing showed no detected lymphoma. The plan is for her to continue acalabrutinib as a single agent maintenance therapy as part of the study.

This “chemo free” approach is likely to be a standard of care for mantle cell lymphoma in the future, particularly for patients with TP53 mutation

Case highlights

Dr. Hill shared several takeaways from this case:

Consult with disease specialists for rare diseases. “Especially for less common diseases, it’s prudent to discuss cases like this with disease specialists,” says Dr. Hill. “The standard of care changes rapidly, and it’s difficult to stay up to date with all the changes in a community setting where you’re managing multiple diseases.”

Having a deep roster of specialists improves care. Dr. Hill specifically highlighted his outstanding colleagues at main campus, Drs. Caimi, Brooks, Winter, Jagadeesh, Dean and Bezerra, who all focus specifically on lymphoma. In addition to seeing patients and leading research studies, they run a weekly Lymphoma Tumor Board for complex cases. These insights are essential in a fast-moving field like lymphoma where the treatment landscape is shifting rapidly.

MRD testing is increasingly used clinically and in research studies to attain a more sensitive assessment of the depth of remission. MRD negativity correlates with a longer duration of response. “The patient achieved a deep remission, which we typically wouldn’t expect in this situation if she had received chemotherapy, explains Dr. Hill.”

The Institute’s hematopathologists keep up to date with the latest molecular testing and all indications. “TP53 testing for mantle cell lymphoma is now standard for Cleveland Clinic patients,” says Dr. Hill.

A strong research team makes a difference for patients. Dr. Winter, the principal investigator of the clinical trial, and the research nurses were instrumental in the patient’s care. Specifically, Sarah Billy, RN, made a big impression on the patient and her family for her attention to detail and close follow-up.

Rotterdam, Munich.

Our initiatives in collaboration with cities include mobility
research and piloting solutions, making driving and traffic more
efficient, while reducing congestion. Mobility behavior is an
important aspect for cities, especially regarding driving and parking
vehicles in urban areas. That is why we research how to make the
mobility behavior of our customers more city-friendly, tailored to
their individual needs. Through strategic collaborations, such as with
the city of Rotterdam, both parties gain deep insights into what the
city needs, and which solutions work well with drivers. Our research
shows that mobility behavior can be effectively influenced by nudging,
or in other words, the positive motivation of people.

Through attractive digital experiences, we aim to enhance the driving
experience and encourage our customers to use their vehicles more
efficiently. Recently, three pilots based on relatively small but
positive incentives have been completed. The insights from these are promising.

Highlights.

The research project named “My Travels”, conducted throughout the
Netherlands in the second half of 2024 with BMW models, provided a
report to users about the length of their trips made and offered
information on realistic alternatives such as travel by foot, bicycle,
or public transport. The results showed that simply gaining insight
into one’s own travel behavior, including information on the length of
trips and alternative travel options, provides incentives to choose an
alternative mode of transport instead of the car. This result aligns
perfectly with Rotterdam’s goal to free up roads for those who truly
need to use them.

Additionally, we implemented a pilot with a gamification approach to
reduce the footprint of our products in the use phase. Real world data
from a representative BMW and MINI fully electric fleet show that
driving in the efficient driving mode generally results in an average
energy consumption reduction of about 7%. The “MINI Artwork Challenge”
pilot’s aim was to stimulate drivers to switch to this mode. It was
conducted in the first quarter of this year in the latest generation
fully electric MINI models Countryman and Cooper, exploring whether
gamification can encourage more energy-efficient driving behavior. In
this pilot, the virtual artwork – an AI generated image — grew larger
the more the user drove in the efficient driving mode. The pilot
results show this encouraged participants to increase their share of
trips in the efficient driving mode by 60% compared to the baseline phase.

Finally, the research project “COOL” (CO₂ Optimal
Charging) was a field experiment that started in April 2025. Its goal
was to provide plug-in hybrid and EV drivers with insights into
charging behavior and the associated CO₂ emissions. By
using a simple and insightful app that shows CO₂ emissions per kWh of
the local electricity mix in real time and alerts the user when they
drop below a certain value, we support drivers in deciding when to
charge their vehicles.

In total, 355 drivers of electric and plug-in hybrid BMW models
participated in this project, which brought at least two valuable
results. Gamification increased CO₂-improved EV charging by 6% and it
suggests that even participants who are already environmentally
conscious are still willing to take additional steps to reduce their
CO₂ impact by charging their vehicles CO₂ improved.

The city of Rotterdam and BMW Group will use the insights gained to
develop more sustainable, user-oriented mobility concepts that improve
both individual mobility and the urban mobility ecosystem.

Background and details of “My Travels Distances & Alternatives”.

This research project originated from a bachelor thesis supervised by
the University of Münster. Erasmus University Rotterdam was involved
as the regular research partner of BMW Netherlands in the design and
analysis of the feedback survey.

Three hundred participants, drivers of BMW and MINI models across the
country, were provided with a test app that offered a clear view of
travel habits, at a more detailed level than the “My Trips” feature
already known to BMW and MINI customers from the My BMW and MINI app.

The app contains two elements: Distances and Alternatives. The first
offered the driver transparency of their car trips. A pie chart
allowed app users to see at a glance how many trips they made weekly
of up to 1 kilometer, 1-5 kilometers, and 5 kilometers or more.
Alternatives provided insight into which realistic alternatives would
have been possible for specific trips: by foot, bicycle, or public
transport, including any distance and/or time savings.

The research question was: do active app users reduce more trips
based on the travel report and recommendations for alternative modes
of transport than inactive users?

Results of “My Travels Distances & Alternatives”.

Overall, analysis indicated that active users of the app reduced one
car trip weekly compared to participants who did not use the app. This
means that simply gaining insight into one’s own travel behavior and
information on alternative travel options provides incentives to leave
the car unused once a week, potentially reducing traffic congestion in
the city.

Zooming in on weekly trips, the reduction in car usage was even
slightly larger: active users made an average of 1.5 fewer trips (of
up to five kilometers). In other words, more than one short trip was
avoided. No significant decrease in car usage was seen on weekends.

Factors influencing participants’ choices related to timing (weekday
or weekend), weather conditions, and personal situation (with or
without children). This emerged from the comprehensive survey that was
part of the research. When asked which types of trips participants
were most inclined to swap for alternative transport, the top three
were: 1) to a park, restaurant, etc., 2) to the gym, 3) to the
supermarket. Picking up and dropping off children remains preferred by
car, as indicated by the last place in the ranking.

When asked about the three main reasons to leave the car unused, the
top three were: 1) travel duration, 2) convenience and availability of
alternative modes of transport, 3) weather conditions.

Background and details of the “MINI Artwork Challenge”.

This pilot resulted from a graduation project within the BMW Group’s
development department, which designs (product) solutions in the field
of energy and sustainable/urban mobility, part of the “Connected
Company”. An overarching goal of many of their projects is to promote
efficient driving habits to support potential reductions of CO₂
emissions in the use phase. The “MINI Artwork Challenge” aimed
to “achieve a lasting change in driving behavior through artistic incentives”.

130 participants took part in the pilot. These drivers were rewarded
for using the efficient driving mode of their MINIs. The more
frequently this mode was used, the further an AI-generated artwork
(consisting of stylized plants or animals) evolved. The image was then
displayed on the central screen at the start of each trip.

Results of the “MINI Artwork Challenge”.

Real world data from a representative BMW and MINI fully electric
fleet show that driving in the efficient driving mode generally
results in an average energy consumption reduction of about 7%. The
“MINI Artwork Challenge” encouraged participants to increase their
share of trips in the efficient driving mode to almost 40%, compared
to 25% in the baseline phase. This corresponds to a 60% increase in
trips in the efficient driving mode.

Background and details of the “COOL” pilot.

We saw there are still some gaps to address in the field of smart
charging. Currently, smart charging enables cost-efficient charging
only at home, but optimal charging technologies are not yet widely
available in the electric vehicle market. Additionally, there is a
lack of awareness about the impact of charging behavior on the
CO₂ footprint of an electric car. While price-optimized
charging is available for dynamic charging tariffs, it often lacks
optimization aimed at reducing CO₂ emissions.

Our idea was to provide clear CO₂ information about the
country’s electricity mix to users, enabling them to shift their
charging to timeslots that are better in terms of CO₂
emissions over a longer cycle. By applying the nudge concept, we
aimed to encourage and steer beneficial charging behavior. Ultimately,
this approach should contribute to reducing the CO₂
footprint in both public and private spaces.

The research question was: how can nudges effectively influence the
timing of electric vehicle charging to align with periods in which the
use of renewable energy sources is higher?

The pilot project, conducted from April to July 2025, involved BMW
355 electric vehicle drivers in the Netherlands. A digital charging
feature called “COOL” was made available in Dutch and English through
the 360° Mobility app on iOS. This simple and insightful app showed
the CO₂ emissions per kWh of electricity in real-time and
alerting the user when it dropped below a certain value. Charging and
vehicle data from all registered participants were collected on BMW
Labs. Additionally, qualitative interviews were conducted with 14
participants to gather in-depth insights.

Results of the “COOL” pilot.

A total of 13.153 charging sessions were analyzed, and timeslots with
a cleaner energy mix were identified on 67 out of 87 days. Through
gamification, we successfully encouraged participants to shift their
charging sessions to time slots with a forecasted higher share of
renewables in the Dutch energy mix, achieving a 6% increase in such
charging sessions compared to the control group. In contrast,
providing forecasts and statistics alone had no significant effect.
Plug-in hybrid drivers were less likely to change their charging
behavior. Customers expressed three things:

• a preference for easy or automatic integration into their routines.
• technical alignment with existing energy applications.
• having a single source of information for optimal timeslots.

The post pilot survey with 90 participants also revealed a valuable
insight. When asked if the participant ‘would be willing to make an
extra effort to charge with reduced CO₂ emissions, such as
by setting a charging window in their app’, 73% of participants
answered “yes”.  Notably, 62% of these environmentally motivated
participants already have a green electricity contract. This indicates
that even those who are already committed to sustainable energy use
are open to taking additional steps to further reduce their CO₂
impact through charging in low-emission windows.

“Smart City Travel” Pilot as a Forerunner to “My Travels”.

In 2022, Rotterdam and BMW launched the Smart City Travel pilot. This
project focused on motorists who (regularly) drove from outside toward
the inner city of Rotterdam. BMW Group, Rotterdam, and the Erasmus
University Rotterdam investigated ways to entice motorists to park
their cars at a park-and-ride (P+R) on the outskirts of the city and
continue the last mile of their journeys using public or shared
transport. The question was: what is needed to motivate BMW drivers to
make this choice in advance and then actually switch modes when an
alternative mode is actively offered in the navigation?

Results showed that information about alternative transport should
not only arrive in the car after the trip starts, as people are not
prepared for it or, for practical reasons (no coat, too many
belongings), cannot or do not want to switch. This led to the idea of
focusing more on transparency and providing drivers with insight into
their trips and offering alternatives as desired (before or after a
trip) in an app.

Collaboration with Rotterdam Since 2018.

A safe, healthy, and livable city is high on the agenda of the
Rotterdam municipality. This requires a new vision of future mobility,
where sustainability, traffic safety, accessibility, and flow play a
crucial role. Since 2018, BMW Group and the City of Rotterdam have
been working together to realize these shared ambitions and pilot
mobility solutions around integrating the car into the ecosystem of a
livable city.